Effect of circulating tumor cells in clinically stable patients on the conundrum of recurrence with cellular residual disease.

Abstract

e15040 Background: Despite no evidence of disease by radiological imaging, up to 30% breast cancer cases are known to relapse after treatment with a curative intent. The presence of CTCs in stage I-II cancer patients signals the activation of extravasation and invasion process leading to micro-metastasis and may lead to poor outcome. CTCs in blood circulation at any stage of cancer indicate detectable Minimal Cellular Disease (MCD). Thus the longitudinal investigation of patients with such biomarker remains highly implicative to predict the recurrence, therapy escalations, and dose modifications. The expression of Program Death - Ligand 1 (PD-L1) on CTCs is a dynamic biomarker and they may escape the elimination by immune system, indicative of progression of metastatic signature. Methods: Retrospectively, ina cohort of 20 cancer patients (e.g. lung, colon-rectal, breast, stomach, etc.) who recently underwent treatment were investigated for the presence of CTCs using CDSCO approved OncoDiscover platform having multi-components conjugated with anti EpCam antibody on magnetic nanoparticles. All patients represented clinically stable disease from previous radiological findings. CTCs enumeration assay was performed using CD45, EpCAM+, and CK18 and over-expression of PD-L1 in1.5 ml of peripheral blood using automated motorized Zeiss fluorescence microscopy. Results: In spite of 'no radiological' findings with clinically stable disease, out of 20 selected patients, 75% (n=15) showed at least 1 CTC. While, 55% (n=11) patients were detected with 1 CTC, 5% patients (n=1) with 2 CTCs, and 15% patients (n=3) were identified with 3 CTCs. In addition, 50% (n=10) of patients demonstrated with PD-L1 expression on CTCs; 1 patient exhibited a CTC cluster. Conclusions: Patients showed CRD in spite of a stable disease, which is an indication of progression of localized disease transforming from primary to secondary. The longitudinal monitoring of patients for CTCs with PD-L1 expression may reveal ‘real time’ residual disease, progression, regression, and actual response to the treatment. CRD monitoring can improve the curative intent by improving PFS and OS in solid cancers.