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Introduction and outline of this thesis111The overall aim of this thesis is to improve the treatment methods for pancreatic and esophagogastric cancer.Part One: Pancreatic cancerThe incidence of pancreatic cancer in the Netherlands has doubled in the last 30 years to approximately 2800 new yearly cases and patients face the lowest survival rate of all solid tumors in the Netherlands according to the Netherlands Cancer Registry (NCR), Netherlands Comprehensive Cancer Organization (https://www.cijfersoverkanker.nl). Most patients present with either locally advanced (unresectable) or metastatic disease (1) and only 15 to 20% of patients are eligible for up-front surgery (2). Known risk factors for pancreatic cancer are a genetic predisposition and environmental risk factors including tobacco use, diet, alcohol consumption, and high caloric intake (3, 4). Staging and management of pancreatic cancer is multidisciplinary. Resection alone typically results in a 5-year overall survival (OS) rate of approximately 10%. However, the prognosis for patients with resected pancreatic ductal adenocarcinoma (PDAC) was notably enhanced with the addition of adjuvant chemotherapy with gemcitabine (5). Adjuvant chemotherapy with 5-fluorouracil (5-FU), folinic acid, irinotecan and oxaliplatin (modified FOLFIRINOX) vs gemcitabine further improved median OS (53.5 vs 35.5 months) after 5 years follow up (6). The optimal neoadjuvant treatment schedule with either chemotherapy alone or chemotherapy in combination with radiotherapy (CRT) for patients with resectable and borderline resectable tumours is under investigation and preferably given in the context of a clinical trial. Neoadjuvant gemcitabine-based CRT achieved a 15% improvement of 5 year OS for patients with resectable or borderline resectable tumors in the PREOPANC trial (7). The PREOPANC-2 trial compared total neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based CRT and adjuvant gemcitabine in patients with the same tumor characteristics as in the PREOPANC-1 trial and interestingly neoadjuvant FOLFIRINOX did not improve OS or resection rates compared to gemcitabine based CRT (OS 21.9 vs. 21.3 months; HR 0.87; 95% CI 0.68-1.12, p=0.28; resection rates 77% vs. 75%, p=0.69) (8). Pancreatic cancer without distant metastasis is unresectable when there is over a 270%u00b0 encasement of the superior mesenteric or portal vein, or more than 90%u00b0 tumor