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Introduction and outline of this thesis151Part two: Esophageal and gastric cancerAround 4000 patients were diagnosed in 2022 with esophageal and gastric cancer in the Netherlands. While the incidence of adenocarcinoma of the esophagusis increasing, the incidence of squamous cell carcinoma of the esophagus is decreasing. The incidence of gastric carcinoma also decreased from around 2000 new patients yearly in 1998 to 1100 patients in 2022. Around one third of patients with esophageal cancer (EC) and nearly half of patients with gastric cancer (GC) are diagnosed in an advanced stage without curative options according to data from the NCR, IKNL (https://www.cijfersoverkanker.nl). Important risk factors for esophageal adenocarcinoma (EAC) are obesity and reflux (31) while Helicobacter pylori infection and family history of gastric cancer are two important risk factors for gastric cancer (32, 33). Like pancreatic cancer, most patients with resectable esophageal and gastric cancer cannot be cured with surgery alone. Preoperative CRT with carboplatin and paclitaxel compared to surgery alone improved the ten-year survival rate of patients with resectable esophageal or esophagogastric-junction cancer from 25 to 38 percent (HR 0.7) (34, 35) and this is currently the standard treatment. Recently the CheckMate 577 trial showed adjuvant immunotherapy with nivolumab to be associated with a longer disease free survival (DFS) compared to placebo (22,4 vs. 11, 0 months, HR: 0,69; p < 0,001) (36). Treatment with CRT without resection can be a good treatment option to improve survival for patients in a good clinical condition who present with locally advanced irresectable esophageal or esophagogastric-junction cancer (37). Patients with resectable gastric cancer do also benefit of systemic treatment before resection. In the MAGIC trial 3 preoperative and 3 postoperative cycles of epirubicin, cisplatin, and 5-FU (ECF) in combination with resection vs. resection alone resulted in a better OS (HR 0.75; 5 year OS: 36 versus 23 percent) (38). Perioperative chemotherapy with the docetaxel-based triplet perioperative FLOT (5-FU plus leucovorin, oxaliplatin and docetaxel) chemotherapy schedule further improved OS to a median 50 months vs 35 months (HR 0.77) with perioperative ECF/ECX (epirubicin, cisplatin and 5-FU or capecitabine) (39) and this is therefore the current standard therapeutic approach for patients with resectable gastric cancer. Palliative treatment for advanced esophageal and gastric cancer frequently consists of combination chemotherapy and/or radiotherapy. The goals of palliative systemic chemotherapy are survival benefit and relief of cancer-related symptoms (31, 40). First-line treatment with oxaliplatin and capecitabine is presently the most commonly employed approach for patients with advanced or metastatic