Prevalence and number of circulating tumour cells and microemboli at diagnosis of advanced NSCLC

Purpose: Timing and magnitude of blood release of circulating tumour cells (CTC) and circulating tumour microemboli (CTM) from primary solid cancers are uncertain. We investigated prevalence and number of CTC and CTM at diagnosis of advanced non-small cell lung cancer (NSCLC).

Methods: Twenty-eight consecutive patients with suspected stage III-IV lung cancer gave consent to provide 15 mL of peripheral blood soon before diagnostic CT-guided fine-needle aspiration biopsy (FNAB). CTC and CTM (clusters of ≥3 CTC) were isolated by cell size filtration (ScreenCell), identified and counted by cytopathologists using morphometric criteria and (in 6 cases) immunostained for vimentin.

Results: FNAB demonstrated NSCLC in 26 cases. At least one CTC/3 mL blood (mean 6.8 ± 3.7) was detected in 17 (65 %) and one CTM (mean 4.5 ± 3.3) in 15 (58 %) of 26 NSCLC cases. No correlation between number of CTC or CTM and tumour type or stage was observed. Neoplastic cells from both FNA and CTC/CTM were positive for vimentin but heterogeneously.

Conclusions: CTC can be detected in two-thirds and CTM in more than half of patients with advanced NSCLC at diagnosis. Reasons underlying lack of CTC and CTM in some advanced lung cancers deserve further investigations.

Circulating Tumor Cells in Diagnosing Lung Cancer: Clinical and Morphologic Analysis

Background: The purpose of this study was to evaluate the value of circulating non-hematologic cells to differentiate benign from malignant lung lesions and their comparison with clinico-histologic features of corresponding primary lesions.

Methods: Circulating cells were isolated by size method from peripheral blood of 77 patients with malignant (n = 60) and benign (n = 17) lung lesions. They were morphologically classified as cells with malignant feature; cells with uncertain malignant feature; and cells with benign feature; then statistically correlated with clinico-cytopathologic characteristics of corresponding lung lesion.

Results: Malignant circulating cells were detected in 54 of 60 (90%) malignant patients, and in 1 of 17 (5%) benign patients; benign circulating cells in 1 of 60 (1%) malignant patients and in 15 of 17 (88%) benign patients; and circulating cells with uncertain malignant aspect in 5 of 60 (8%) malignant patients and 1 of 17 (5%) benign patients. For a malignant circulating cells count greater than 25, sensitivity and specificity were 89% and 100%, respectively. The count was significantly correlated with stage, size, and standard uptake value of primary tumor. In 39 of 54 (72%) cases, the malignant circulating cells allowed a specific histologic diagnosis of the corresponding primary tumor after immunohistochemical analysis.

Conclusions: Malignant circulating cells may be a valid marker in the diagnostic workup of lung lesions. However, our resuts should be corroborated by larger future studies especially for patients having small nodules.

Circulating tumour cells in patients with lung cancer undergoing endobronchial cryotherapy

Early diagnosis of lung cancer still poses a major issue, with a large proportion of patients diagnosed at late stages. Therapeutic options and treatment remain limited in these patients. In most cases only palliative therapies are available to alleviate any severe symptoms. Endobronchial cryotherapy (EC) is one form of palliative treatment offered to patients with obstructive airway tumours. Although successful, the impact on circulating tumour cell (CTCs) spread has not been investigated in detail. This study recruited 20 patients awaiting EC treatment. Baseline and post EC blood samples were analysed for presence of CTCs. Results showed an increase in CTCs following EC in 75% of patients. Significant increases were noticeable in some cases. Although EC is a well-accepted modality of treatment to alleviate symptoms, it may lead to an increase in CTCs, which in turn may have implications for tumour issemination and metastatic spread.

Circulating Tumour Cells in Patients with Malignant Lung Tumors Undergoing Radio-frequency Ablation

Background/Aim: Radiofrequency ablation (RFA) is an increasingly utilised technique in patients with surgically-untreatable lesions. The effect of this therapy on circulating tumor cells (CTCs) is unknown. As far as we are aware of, this is the first study to evaluate the effects of RFA on CTCs in patients with malignant lung tumors immediately post-treatment. Patients and Methods: Nine patients with primary or metastatic lung tumors underwent RFA therapy from June to November 2013. Blood samples were taken before and after RFA, and filtered through the ScreenCell CTC capture device. Results: A general increase in CTCs in 7 out of the 9 cases was found, the largest increases were seen in the metastatic group. Conclusion: This study demonstrates that the manipulation and ablative procedure of lung tumors leads to immediate dissemination of tumor cells, the effects of which are unknown and require further investigation.

An assessment of diagnostic performance of a filter-based antibody-independent peripheral blood circulating tumour cell capture paired with cytomorphologic criteria for the diagnosis of cancer. Lung Cancer

Objectives: Circulating tumour cells (CTCs) are reported to be predictive for prognosis and response to treatment in advanced lung cancer. However, the clinical utility of the CTCs detection remains unknown for early stage lung cancer as the number of CTCs is reported as low, providing challenges in identification. We have evaluated diagnostic performance of filtration-based technology using cytomorphologic criteria in patients undergoing surgery for lung cancer.

Material and methods: We processed blood from 76 patients undergoing surgery for known or suspected lung cancer using ScreenCell(®) Cyto filter devices. Captured cells were stained using haematoxylin and eosin and independently assessed by two pathologists for the presence of atypical cells suspicious for cancer. Diagnostic performance was evaluated against pathologist reported diagnoses of cancer from surgically obtained specimens.

Results: Cancer was diagnosed in 57 patients (77.0%), including 32 with primary lung cancer (56.1%). The proportion of patients with early stage primary lung cancer in which CTCs were identified was 18 and 21 (56.3% and 65.6%, respectively) as reported by two pathologists. The agreement between the pathologists was 77.0% corresponding to a kappa-statistic of 53.7% indicating moderate agreement. No significant differences were found for the percentage of CTCs for primary and metastatic cancer as well as for cancer stages. On sensitivity weighted analysis, a sensitivity and specificity were 71.9% (95% CI 60.5-83.0) and 52.9% (95% CI 31.1-77.0), respectively. On specificity weighted analysis, a sensitivity and specificity were 50.9% (95% CI 39.3-64.4) and 82.4% (60.4-96.2), respectively.

Conclusion: The performance of the tested filter-based antibody-independent technology to capture CTCs using standard cytomorphologic criteria provides the potential of a diagnostic blood test for lung cancer.