Association of a Combined Cancer Exhaustion Score with Circulating Tumor Cells and Outcome in Ovarian Cancer—A Study of the OVCAD Consortium

SIMPLE SUMMARY: Advances in circulating tumor cells (CTCs) research could improve the way we diagnose, treat and monitor epithelial ovarian cancer (EOC) patients. In this study, we investigated the interplay between inflammation-induced systemic catabolic markers and the presence of CTCs and patient outcome, and showed that the presence of CTCs goes hand-in-hand with an increased protein turnover and immune activation. We integrated the information provided by measuring the plasma levels of albumin, tryptophan and its metabolite kynurenine in a combined score for cancer exhaustion (CCES). Our study indicates that not only could the CCES be a useful prognostic biomarker in women with EOC, but also that the interaction between the systemic microenvironment and CTCs is worth investigating in further studies. ABSTRACT: We investigated the prognostic role of systemic characteristics for cancer exhaustion and the presence of circulating tumor cells (CTCs) in primary epithelial ovarian cancer (EOC) patients. We included 185 patients in this multicenter study with a median follow-up time of 10.25 years. Albumin, c-reactive protein (CRP) and the kynurenine to tryptophan ratio (Kyn/Trp) as well as the CTC-related marker cyclophilin C (PPIC) were obtained before primary therapy and were correlated to the respective clinical and outcome data. The information provided by albumin and Kyn/Trp was integrated in a combined score for cancer exhaustion (CCES). A high CCES characterized by hypoalbuminemia and a high Kyn/Trp was associated with both decreased overall and progression-free survival, independent from other known prognostic factors in a multivariable analysis. The presence of PPIC-positive CTCs was significantly associated with a high CCES, highlighting that the interplay between the systemic microenvironment and CTCs should be considered in “liquid biopsy” biomarker assessment.