Response to and Survival after First-Line FOLFIRINOX or Gemcitabine/Nab-Paclitaxel for Localized Pancreatic Ductal Adenocarcinoma

Abstract

Objectives: To investigate the immune micro-environment in tumors of patients with pancreatic ductal adenocarcinoma (PDAC) after immediate surgery or neoadjuvant therapy and its relation to survival outcome. Methods: We analysed tumor samples from 50 patients without and 53 patients with neoadjuvant chemo-radiotherapy. Immune profiling of FFPE tumor samples was performed using the NanoString PanCancer assay and the expression of 770 immune related genes was measured. We used the two sample T-test for comparison of gene expression levels between the two groups. The multivariate Cox proportional hazards model was performed to identify independent prognostic predictors. The Kaplan-Meier method with a log-rank test was applied to compare the survival distributions between groups. Results: Total tumor infiltrating lymphocytes (TILs) was equally distributed between treatment groups. B cell infiltration was decreased significantly (p< 0,001) in the neoadjuvant group, whereas T cell infiltration did not vary between groups. Furthermore, CXCL12 expression, a chemokine involved in tumor proliferation and progression, was significantly (p< 0,0001) higher in neoadjuvant treated tumors. However, its receptor CXCR4 was down regulated. In addition, high expression of the ALCAM gene was strongly associated with poor prognosis in both treatment

Response to the Comment on “Postoperative Chemotherapy Benefits Patients Who Received Preoperative Therapy and Pancreatectomy for Pancreatic Adenocarcinoma”

“…When it is not, we generally administer 2 to 4 months of systemic chemotherapy with either FOLFIRINOX or gemcitabine plus nab-paclitaxel as the initial therapy. 8 We base the duration of treatment on parameters evaluated prior to treatment and upon restaging; in general, longer durations of chemotherapy are administered to patients who have radiographic or serologic evidence of response. 9 We selectively administer (chemo)radiation to patients who are felt to be at high risk for margin-positive resections and generally continue to recommend pancreatectomy to patients who have no evidence of disease progression following therapy.…”