Approximately 60% of patients initially treated for squamous cell cancer of the upper gastrointestinal tract suffer from advanced tumor disease (UICC stages III and IV). Multimodal strategies lead to overall survival rates of up to 50%. Recent studies show indications that the risk of distant metastases after induction chemotherapy (CT) is less than after primary radiotherapy (RT) or radiochemotherapy (RCT). Hyperfractionation or accelerated radiation with concomitant boost shows superior results compared to classic RT. Intensity-modulated radiotherapy (IMRT) is a new method for better adjusted dose distribution. Targeted therapy with specific antibodies against biological targets, such as epidermal growth factor receptor (EGFR), showed superiority over RT but the comparison to classic RCT is still pending. Targeted therapy against vascular endothelial growth factor (VEGR) showed antiangiogenetic effects on tumors. In cases of non-resectability or distant metastases, palliative CT and target therapy are recommended. Reirradiation or IMRT offer increased locoregional tumor control at the expense of higher toxicity. Overall, advances in research on tumor biology offer increasingly more prognostic factors and markers for customized individual targeted therapy and CT.
