title: Potential predictive role of chemotherapy-induced changes of soluble CD40 ligand in untreated advanced pancreatic ductal adenocarcinoma.
abstract: Pancreas ductal adenocarcinoma lacks predictive biomarkers. CD40 is a member of the tumor necrosis factor superfamily. CD40-sCD40L interaction is considered to contribute to the promotion of tumor cell growth and angiogenesis. The aim of the present study was to investigate the role of serum sCD40L as a predictor in metastatic pancreatic cancer. We evaluated 27 consecutive pancreatic cancer patients treated with FOLFIRINOX (21 patients) or gemcitabine plus nab-paclitaxel combination (six patients). The sCD40L level was measured in serum by enzyme-linked immunosorbent assay at baseline, at first evaluation (all patients), and at time to progression (18 patients). The radiological response was evaluated according to the Response Evaluation Criteria in Solid Tumors, Version 1.1. The Wilcoxon signed-rank test was used to compare pre-post treatment sCD40L levels with respect to clinical response, while Pearson's correlation coefficient was used for the correlation between sCD40L and CA19.9 pre- and post-treatment. The Kruskal-Wallis test was also conducted for further comparisons. We observed a statistically significant reduction in the sCD40L level after 3 months of treatment in patients with partial response (11,718.05±7,097.13 pg/mL vs 4,689.42±5,409.96 pg/mL; P<0.01). Conversely, in patients with progressive disease, the biomarker statistically increased in the same time (9,351.51±7,356.91 pg/mL vs 22,282.92±11,629.35 pg/mL; P<0.01). This trend of sCD40L was confirmed in 18 patients at time to progression after the first evaluation. No differences were recorded within the stable disease group. Moreover, there was a positive correlation between the sCD40L and CA19.9 pre-post treatment variation percentage (Pearson's correlation coefficient =0.52; P<0.05). Our data suggest a possible predictive role of sCD40L in pancreatic cancer patients, similar to CA19.9.
authors.affiliation: Preclinical and Clinical Pharmacology Unit.
authors.forename: Amalia
authors.initials: A
authors.lastname: Azzariti
authors.affiliation: Medical Oncology Unit.
authors.forename: Oronzo
authors.initials: O
authors.lastname: Brunetti
authors.affiliation: Preclinical and Clinical Pharmacology Unit.
authors.forename: Letizia
authors.initials: L
authors.lastname: Porcelli
authors.affiliation: Scientific Direction, National Cancer Research Centre, Istituto Tumouri "Giovanni Paolo II", Bari.
authors.forename: Giusi
authors.initials: G
authors.lastname: Graziano
authors.affiliation: Preclinical and Clinical Pharmacology Unit.
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Iacobazzi
authors.affiliation: Medical Oncology Unit.
authors.forename: Michele
authors.initials: M
authors.lastname: Signorile
authors.affiliation: ARC-NET Research Centre, University of Verona, Verona, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: Medical Oncology Unit.
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.affiliation: Medical Oncology Unit.
authors.forename: Nicola
authors.initials: N
authors.lastname: Silvestris
keywords: FOLFIRINOX; gemcitabine plus nab-paclitaxel; pancreatic ductal adenocarcinoma; predictive factor; soluble CD40 ligand