Serum cytokine levels are associated with tumor progression during FOLFIRINOX chemotherapy and overall survival in pancreatic cancer patients

Background: Biomarkers predicting treatment response may be used to stratify patients with pancreatic ductal adenocarcinoma (PDAC) for available therapies. The aim of this study was to evaluate the association of circulating cytokines with FOLFIRINOX response and with overall survival (OS). Methods: Serum samples were collected before start and after the first cycle of FOLFIRINOX from patients with PDAC (n=83) of all disease stages. Overall, 34 circulating cytokines were analyzed with a multiplex immunoassay. In addition, changes in peripheral blood immune cell counts were determined by flow cytometry to correlate with differences in cytokine levels. Chemotherapy response was determined by CT scans with the RECIST 1.1 criteria, as disease control (n=64) or progressive disease (n=19) within eight cycles of FOLFIRINOX. Results: Patients with high serum IL-1RA concentrations after one cycle of chemotherapy were less likely to have tumor progression during FOLFIRINOX (OR 0.25, P=0.040). Increase of circulating IL-1RA concentrations correlated with increase of total, classical (CD14+CD16-), and non-classical monocytes (CD14-CD16+), and dendritic cells. In multivariable cox regression, including the variables chemotherapy response outcome and baseline CA19-9 level, serum concentrations of IL-7 (HR 2.14, P=0.010), IL-18 (HR 2.00, P=0.020), and MIP-1β (HR 0.51, P=0.025) after one cycle of FOLFIRINOX showed correlations with OS. Conclusions: Circulating IL-1RA, IL-7, IL-18, and MIP-1β concentrations are biomarkers associated with FOLFIRINOX response in PDAC patients, suggesting an important role for specific immune cells in chemotherapy response and PDAC progression. Cytokine-based treatment might improve patient outcome and should be evaluated in future studies

The impact of cancer treatment on quality of life in patients with pancreatic and periampullary cancer: a propensity score matched analysis

Background: The impact of pancreatic and periampullary cancer treatment on health-related quality of life (HRQoL) is unclear. Methods: This study merged data from the Netherlands Cancer Registry with EORTC QLQ-C30 and -PAN26 questionnaires at baseline and three-months follow-up of pancreatic and periampullary cancer patients (2015–2018). Propensity score matching (1:3) of group without to group with treatment was performed. Linear mixed model regression analyses were performed to investigate the association between cancer treatment and HRQoL at follow-up. Results: After matching, 247 of 629 available patients remained (68 (27.5%) no treatment, 179 (72.5%) treatment). Treatment consisted of resection (n = 68 (27.5%)), chemotherapy only (n = 111 (44.9%)), or both (n = 40 (16.2%)). At follow-up, cancer treatment was associated with better global health status (Beta-coefficient 4.8, 95% confidence-interval 0.0–9.5) and less constipation (Beta-coefficient −7.6, 95% confidence-interval −13.8–1.4) compared to no cancer treatment. Median overall survival was longer for the cancer treatment group compared to the no treatment group (15.4 vs. 6.2 months, p < 0.001). Conclusion: Patients undergoing treatment for pancreatic and periampullary cancer reported slight improvement in global HRQoL and less constipation at three months-follow up compared to patients without cancer treatment, while overall survival was also improved

Serum mir-373-3p and mir-194-5p are associated with early tumor progression during folfirinox treatment in pancreatic cancer patients

In this study, we explored the predictive value of serum microRNA (miRNA) expression for early tumor progression during FOLFIRINOX chemotherapy and its association with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 132 PDAC patients of all disease stages were included in this study, of whom 25% showed progressive disease during FOLFIRINOX according to the RECIST criteria. MiRNA expression was analyzed in serum collected before the start and after one cycle of chemotherapy. In the discovery cohort (n = 12), a 352-miRNA RT-qPCR panel was used. In the validation cohorts (total n = 120), miRNA expression was detected using individual RT-qPCR miRNA primers. Before the start of FOLFIRINOX, serum miR-373-3p expression was higher in patients with progressive disease compared to patients with disease control after FOLFIRINOX (Log2 fold difference (FD) 0.88, p = 0.006). MiR-194-5p expression after one cycle of FOLFIRINOX was lower in patients with progressive disease (Log2 FD −0.29, p = 0.044). Both miRNAs were predictors of early tumor progression in a multivariable model including disease stage and baseline CA19-9 level (miR-373-3p odds ratio (OR) 3.99, 95% CI 1.10–14.49; miR-194-5p OR 0.91, 95% CI 0.83–0.99). MiR-373-3p and miR-194-5p did not show an association with OS after adjustment for disease stage, baseline CA19-9, and chemotherapy response. In conclusion, high serum miR-373-3p before the start and low serum miR-194-5p after one cycle are associated with early tumor progression during FOLFIRINOX.</p