Neoadjuvant therapy impact in early pancreatic cancer: "bioborderline" vs. "non-bioborderline".

Backgrounds/Aims: To analyze the results of the neoadjuvant treatment of patients in our center with early pancreatic cancer. Methods: Eighty-four patients with early pancreatic cancer (I-II) were included, of which 59 were considered "bioborderline" (carbohydrate antigen [CA] 19-9 > 37 U/L), and 25 were considered "non-bioborderline" (CA19-9 < 37 U/L). The R0 resection rate, presence of negative nodes, survival, and recurrence rates were analyzed in two groups, the NEO group (neoadjuvant + surgery) and the non-NEO group (upfront surgery). Results: A 28.6% pathologic complete response was observed in the NEO group of the whole sample. The residual R0 was 85.7%, and nodes were negative in 78.6% of the patients in the NEO group of bioborderline patients. All non-bioborderline patients treated with neoadjuvant were R0, and no affected nodes were observed in any of them. The median overall survival (OS) in patients with elevated CA19-9 levels in the NEO group was 31.4 months vs. 13.1 months in the non-NEO (log-rank test p = 0.006), with a 62% relative reduction in the mortality rate (hazard ratio = 0.38, 95% confidence interval: 0.20-0.79; p = 0.008). The median OS in patients with normal CA19-9 levels in the NEO group was 65.9 months vs. 16.2 months in the non-NEO group, without statistically significant differences between the two but with a trend toward significance (log-rank test p = 0.08). Conclusions: A neoadjuvant strategy seemed to improve local control and the survival of patients with early pancreatic cancer, both those with elevated CA19-9 and normal marker levels.

From First Line to Sequential Treatment in the Management of Metastatic Pancreatic Cancer.

The current management of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) is based on systemic chemotherapy. The results of the MPACT and PRODIGE clinical trials have demonstrated that the combination of nab-paclitaxel and gemcitabine (GEM) as well as FOLFIRINOX regimen result in improvement in overall survival when compared to GEM alone. Treatment guidelines now recommend either one of these two regimens as first line treatment for fit patients with mPDAC. Because no head-to-head comparison between the two regimens exists, the selection of one versus the other is based on clinical criteria. The design and eligibility criteria of these two clinical trials are dissimilar, making the results of the MPACT trial more applicable to the general population of patients with mPDAC. In addition, the combination of nab-paclitaxel and GEM is better tolerated and easier to administer in clinical practice than FOLFIRINOX. Furthermore, when the regimens are studied in comparable patient populations the efficacy results are very similar. Nanoliposomal irinotecan plus 5FU has recently demonstrated a significant increase in efficacy rates after a GEM-based treatment. Importantly, treatment of mPDAC should now be considered as a continuum care for patients who are fit, with second and even third line treatments. Different sequential treatment algorithms are proposed based on available data. In retrospective studies, patients who were managed with GEM-based regimens followed by fluoropyrimidine-based regimens appear to have the most favorable outcome.