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                                    Summarizing discussion and future perspectives1176samples stored in heparin were available of 68 patients (of the 82 patients who were included in the clinical study between 2004 -2013). From 63 patients a baseline sample was available (14GC; 49EC). A total of 53 follow up samples were available of these 63 patients (12GC; 41EC). Treatment of the samples with heparinase was required to counteract the known interaction between heparin and PCR analysis (53). Expression of ci-miRNA was analyzed in relation to overall survival (OS), progression-free survival (PFS), and response to chemotherapy. ci-miRNA levels were detectable in 36 baseline (71%) samples and in 14 (47%) follow-up samples. A significant relation was found between a high plasma miR-375 expression and a longer OS in patients with EAC treated with first-line palliative chemotherapy with cisplatin and gemcitabine, making this miRNA promising as a prognostic marker for patients with EAC. Increased circulating miR-200c-3p in GC showed a trend (p =0.06) towards a shorter OS. Due to low evaluable sample numbers it was difficult to draw definitive conclusions from this study. No prognostic and/or predictive value was found for the other tested ci-miRNAs in contrast to previously reported literature as described in chapter 5 reflecting the difficulty of reproducible results. No significant difference was observed in ci-miRNA expression between paired pre- and ontreatment samples and ci-miRNA expression was not associated with response to chemotherapy although numbers of available samples were low. While ci-miRNAs show promise as a non-invasive, stable biomarker with prognostic and predictive potential, their clinical application in daily practice requires reliable and precise data from extensive multicenter studies(54). Circulating tumor DNA is another noninvasive biomarker with promising results in different types of esophagogastric cancer(55). Further biomarker development is necessary to optimize patient selection to reduce toxicity of non-effective therapies and reduce treatment costs. This thesis describes four different studies in patients with pancreatic cancer and esophagogastric cancer. The common goal of these studies was to improve the future prospects of patients with pancreatic cancer and esophagogastric cancer either by exploring the added effect of therapeutic interventions (panitumumab added to gemcitabine based CRT (chapter 2) and vitamin B12 and folate suppletion to gemcitabine-cisplatin (chapter 4), re-introduction of FOLFIRINOX chemotherapy after a therapy free interval (chapter 3)), and analyses of putative biomarkers for future patient selection (chapter 5). Despite recent progress in the field further studies are needed to advance the understanding and refine treatment strategies, ultimately improving the prognosis and outcomes for individuals diagnosed with pancreatic cancer and esophagogastric cancer.
                                
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