Search for new predictive/prognostic biomarkers in potentially resectable pancreatic ductal adenocarcinoma

Abstract

Introduction: The mortality rate in pancreatic ductal adenocarcinoma (PDAC) is similar to its incidence rate due to the fact that almost 50% of the patients diagnosed have metastasis and 1-year OS for all stages barely over 20%. For this reason, new biomarkers (BKs) are urgently needed in order to improve outcomes in PDAC patients. Therefore, the main aim of this multicenter and prospective project is to find predictive and/or prognostic BKs. We will be focusing on CHFR (checkpoint with forkhead and ring finger domains) promoter methylation. This has been previously proposed as a predictor to taxane response in several tumors, even though its role in PDAC and/or in patients treated with nab-paclitaxel has not been described yet. On the other hand, there are many cytokines produced in the cancer microenvironment that can nowadays be accurately analyzed and might be used as potential serum BK in PDAC. Methods: Patients diagnosed with potentially resectable PDAC with poor prognostic factors (CA 19.9 > 150 U/mL; suspected micrometastasis or low PS) and treated with neoadjuvant treatment are being prospectively included. Methylation status of CHFR promoter by MSP and pyrosequencing, surgery CHFR IHC, and serial analyses (to diagnosis, with TAC, with surgery and time of relapse/or after 1 year of follow-up) of serum levels of 80 cytokines are being done. Results: Since February 2018, 10 patients with median of age of 63.5 years, mostly men (60%) have been included, with radical surgery performed in 7 of them. Two operated patients are receiving treatment and three operated patients have developed progression of disease. All these patients have received nab-paclitaxel and gemcitabine as neoadjuvant treatment and only two of them have received QTRT. After a median followup of 3 months (3 - 7), perineural and vascular invasion were confirmed after surgery in 57% and 71% of cases, respectively. Positive nodes were found in 57%, with medians of positive and resected nodes being 1 and 26, respectively. Surgical margins were negative (R0) in 57% of cases (43% R1). Pathological response was described as partial in 60%, with no changes in 30%, and progression in 10%. Globally, the OS was 11.9 months (6.7-17.1). In K-M analysis significant differences (P =.028) were observed in cases in which radical surgery had been performed with a mean disease-free survival of 15.2 months (8.9-21.5) and 5.3 months (1.8-8.8) for unresectable patients. Regarding the cytokine array, our preliminary data suggest that there is differential cytokine expression between different stages of the disease. We are currently performing the MSP and pyrosequencing analysis of CHFR promoter in tumoral tissue from operated patients. Conclusion: Cytokine profile may change during disease progression and the correlation of this data with clinical ones will enable us to know if they could be used as BKs. More mature provisional data focused on CHFR methylation and CHFR profile in patients with potentially resectable PDAC treated with neoadjuvant therapy will be presented during ESMO World Congress on Gastrointestinal Cancer 2019.