A retrospective analysis of neuroendocrine tumour of pancreas: a single institute study

Background: The aim of the work was the clinical characteristics and analysis of preliminary results for surgical treatment of pancreatic neuroendocrine tumors (PNETs). This article deals with the classification of the Pancreatic Neuroendocrine Tumors (PNETs) and discusses their presentation, behaviour, treatment and prognosis.Methods: This was a retrospective study of 70 patients of PNET done over a period of 3 years in The Gujarat Cancer and Research Institute, Ahmedabad. 24 patients who underwent surgical treatment for PNET were further evaluated for surgical outcome, 5yr disease free survival and overall survival.Results: In this study of 70 patients, 61(87.14%) were non-functional. Approximately 77% of PNETs were advanced on presentation (57% metastatic and 20% locally advanced). 20 patients had disease resectable on presentation (11 NF + 9 F). These 20 patients belong to stage I and II of TNM staging system. Only 4 out of 40 metastatic diseases had locally resectable tumor. Of 24 patients who underwent surgery, 12 underwent pancreatico-duodenectomy, 6 underwent enucleation and 6 underwent distal pancreatectomy.Conclusions: PNETs are uncommon tumor of pancreatic origin with presentation more commonly in males than females, usually in the 5th decade. Approximately 77% of patients are advanced or metastatic at presentation. Among those resectable, the Overall Survival for FPNETs and NFPNETs was 90% and 94% respectively and 5yr Disease Free Survival for the same was 100% and 84% respectively.

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival