Promising biomarker panel to monitor therapeutic efficacy of neoadjuvant chemotherapy in pancreatic cancer patients

Abstract

Background: Neoadjuvant chemotherapy (NAC) can provide improved survival outcomes in pancreatic ductal adenocarcinoma (PDAC) patients who respond to treatment, but currently available biomarkers cannot reliably predict NAC response. This study aimed to determine the potential of a previously identified diagnostic and prognostic biomarker panel (i.e. Ca-125, S100A2, S100A4, Mesothelin and Ca19-9) for the monitoring of NAC-response in PDAC patients.

Methods: This single-centre, retrospective study, utilised serum from NAC treated PDAC patients to determine the levels of biomarkers by Enzyme-Linked Immunosorbent Assay (ELISA). The percentage of the tumour bed occupied by viable carcinoma (PVC) was used to divide patients into good (PVC < 50%) and poor (PVC ≥ 50%) NAC-responders. Statistical analysis was performed to measure the ability of individual biomarkers and a biomarker panel in NAC treatment response and patient survival.

Results: Serum specimens from a total of 108 PDAC patients were assessed. Ca-125, Ca19-9 and S100A2 showed a significant positive correlation with PVC. Ca-125 demonstrated a superior ability to monitor NAC treatment response (Area under receiver operating curve (AUC): .6954) compared to the more widely used clinical biomarker, Ca19-9 (AUC: .6291). A panel of Ca-125 and Ca19-9 showed good ability to monitor NAC response in PDAC patients (AUC: .7349). Patients with high levels of both Ca-125 and Ca19-9 were shown to have the poorest overall survival (median overall survival: 17 vs. 30 months).

Conclusion: A serum biomarker panel of Ca-125 and Ca19-9 could be used for effective clinical management of PDAC patients undergoing NAC treatment.

Keywords: biomarkers; chemoresistance; neoadjuvant chemotherapy; pancreatic ductal adenocarcinoma; treatment response.