Circulating cytokine levels as biomarkers for response to FOLFIRINOX chemotherapy in pancreatic cancer patients

Abstract

Introduction: FOLFIRINOX chemotherapy is currently standard treatment in patients with advanced pancreatic cancer (PDAC) and is being investigated as neoadjuvant treatment in resectable disease. However, patient stratification is essential, because of the low response to FOLFIRINOX and severe side effects. The balance of tumor-promoting and tumor-suppressing components of the immune system plays a crucial role in cancer progression and treatment response. Cytokines are key players in immune cell signaling. The aim of this study was to identify circulating cytokines as potential biomarkers for FOLFIRINOX response. Methods: Serum samples of 88 PDAC patients were prospectively collected before and after one cycle of FOLFIRINOX chemotherapy. Patients were categorized as disease control patients (DC) or progressive disease patients (PD), based on the RECIST criteria. Cytokine detection rates and concentrations were measured using a 34-plex Luminex immunoassay (Procarta). Results: Before start of treatment, the detection rate of IL-2 was higher in DC compared to PD (21.1% vs 0%, p=0.031), but not after chemotherapy. Only after chemotherapy, the detection rate of IL-1RA was higher in DC compared to PD (50.9% vs 21.1%, p=0.032). The IL-1RA detection rate increased during chemotherapy in DC patients only (1.8% before, 50.9% after, p< 0.001). Moreover, absolute IL-1RA concentrations increased in DC patients (0.00 pg/mL before, 16.85 pg/mL after, p< 0.001), but not in PD patients. Conclusions: IL-2 and IL-1RA are differentially expressed in serum of PDAC patients with DC and patients with PD after FOLFIRINOX chemotherapy. Cytokines are promising biomarkers to aid chemotherapy decision making in PDAC patients.