Individualized Treatment of Patients With Advanced NSCLC: Potential Application for Circulating Tumor Cells (CTC) Molecular and Phenotypical Profiling

The primary aim of the Project is to determine the percentage of CTC-positive patients and total CTC numbers in advanced NSCLC at baseline, before starting treatment.

To valuate CTC count modifications as an early predictor of response to treatment a prospective observational study will be conducted, consecutively enrolling 150 patients regardless of type or line of therapy, which will be reevaluated for disease status and CTC count depending on the type and schedule of treatment.

Furthermore, purified CTC will be obtained by automated platform and DNA sequencing will be performed to assess sensitizing mutations in advanced NSCLC patients. The EGFR mutations or EML4-ALK fusion gene detected in CTC will be compared with those reported for the tumor specimen using standard sequencing.

In parallel, the CTC count assay will be integrated with mAb targeting EGFR or EML4-ALK fusion gene, to test whether assaying the quote of EGFR-positive and ALK-positive CTC provides a more sensitive marker for rating pharmacodynamic effects in patients compared with total CTC counts.

Moreover, it was reported that NSCLC cells with EGFR mutations manifest activation of the PI3K (phosphatidylinositol 3-kinase)-AKT and MEK-ERK (extracellular signal-regulated kinase) signaling pathways under the control of EGFR, and exposure of such cells to EGFR-TKIs blocks signaling by both pathways and induces apoptosis 13. To evaluate whether live vs. apoptotic CTC changes under treatment may be used as predictor of tumor response, M30-positive CTC will be quantified as previously 8.

Data obtained with the CTC assay will be correlated with common prognostic factors.

Inclusion criteria

• Age 18-80 years old, males or females;
• Patients with NSCLC confirmed by histopathology or cytology;
• Life expectancy > 6 months;
• Patients are voluntary to participate and sign the informed contents

Exclusion criteria

• Any condition which might hamper compliance to the schedule of assessments