Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic Treatment

Abstract

In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC) and their utility for therapy monitoring in non-small cell lung cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells) were counted. At baseline 18 (41.9%) patients were positive for intact CTC count and 10 (23.2%) of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ³5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other "objects" such as apoptotic CTC or CK fragments to guide the clinical management of these patients.

Figure 1

Images obtained after blood analysis of a NSCLC patient using CellSearch. We represented a morphological intact CTC (with an orange mark) round-oval, nucleated (DAPI⁺) >4 µm, CD45⁻ and CK⁺; a dual CK⁺ and CD45⁺ cell; an apoptotic CTC with CK⁺, CD45⁻ and DAPI⁺ staining but non standards of size and a CK fragment only with CK⁺ staining and a blood cell CD45⁺, CK⁻ and DAPI⁺.

Figure 2

Kaplan-Meier curves for progression-free survival and overall survival of NSCLC patients grouping patients according to morphological intact CTC levels at baseline.

Figure 3

CTC levels at baseline, 2nd and 5th cycle of chemotherapy.

Figure 4

Kaplan-Meier curves for progression-free survival and overall survival. Only parameters with significant impact in patient outcome are represented. (A) Morphological intact CTC levels at 2nd cycle of chemotherapy; (B) CTC fragments at 2nd cycle of chemotherapy in patients with ≤2 CTC; (C) Changes in morphological intact CTC levels between baseline and 2nd cycle of chemotherapy; (D,E) Morphological intact CTC levels at 5th cycle of chemotherapy for PFS and OS, respectively; (F) Changes in CTC levels between baseline and the 5th cycle of chemotherapy.