Abstract

Tumor proliferation and metastasis are closely related to tumor-induced angiogenesis. For some patients with advanced non-small cell lung cancer (NSCLC), anti-angiogenic therapy combined with chemotherapy can effectively improve the one-year survival rate of the tumor. With the discovery of circulating tumor vascular endothelial cells (CTECs), combined detection of CTCs and CTECs provides a possible monitoring approach for anti-angiogenic therapy. At present, the correlation between anti-angiogenic therapy and the dynamic changes of CTCs and CTECs in peripheral blood is still unknown. Therefore, in this study, the dynamic detection of CTCs and CTECs in peripheral blood is carried out in advanced NSCLC patients, which are undergoing chemotherapy combined with anti-angiogenic therapy, and the correlation with therapeutic effect is further analyzed. Sixteen patients with pathologically confirmed advanced NSCLC (IIIB-IVB) were enrolled in this study. The CTCs and the CTECs were detected by using SE-iFISH technique in peripheral blood. 6.5ml peripheral blood was collected before chemotherapy combined with anti-angiogenic therapy and after 2 cycles. The changes of CTCs and CTECs before and after treatment were compared, and the correlation between CTCs, CTECs and its clinical efficacy and survival was analyzed after 6 cycles of treatment. In16 NSCLC patients, the number of CTCs was 0-20 /6.5ml whole blood (median 5), and the number of CTECs was 0-38 /6.5ml whole blood (median 4) before treatment. After 2 cycles, the number of CTCs was 1-89 /6.5ml whole blood (median 6), and the number of CTECs was 0-21 /6.5ml whole blood (median 4). Of the 16 patients, 7/16 (43.75%) patients' CTCs count decreased after 2 cycles of chemotherapy combined with anti-angiogenic therapy. Only 1 patient had RECIST1.1 system assessment of disease progression (PD), and its disease control rate (DCR) was 85.71% (6/7), which was higher than the DCR 66.67% (6/9) increased by CTCs count. The DCR of 9 patients with decreased CTECs count was 77.78% (7/9), and the median PFS time was 8.3m(7.1m-9.5m), while 3 patients with increased CTECs count developed PD, DCR was only 57.14 (4/7) and the median survival time was 5.2m (3.4m-7.1m) (Log-Rank value was 0.09). In advanced NSCLC treated by chemotherapy combined with anti-angiogenesis therapy, SE-iFISH technique can be used to dynamically observe the quantitative changes of CTCs and CTECs in peripheral blood. The preliminary results suggests that the increase of CTCs and CTECs after chemotherapy combined with anti-angiogenic therapy in NSCLC, especially the increase of CTECs may be closely related to the poor therapeutic effect of anti-angiogenic therapy.

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