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Chapter 6116associated with more side effects compared to capecitabine and oxaliplatin, e.g. a higher incidence of grade 3 to 4 neutropenia, alopecia, thromboembolism, and renal dysfunction while peripheral neuropathy and diarrhea is a more frequent side effect of 5-FU and oxaliplatin (25, 31, 39, 40). Both 5-FU and its prodrug capecitabine are metabolized by the enzyme dihydropyrimidine dehydrogenase (DPD). Patients with a known impaired DPD activity can experience severe toxicity of 5-FU and capecitabine (41). Therefore, the here employed cisplatin and gemcitabine treatment combination may be potentially considered a palliative treatment option for selected patients who cannot tolerate 5-FU or oxaliplatin, although in daily practice cisplatin is often replaced by carboplatin to reduce toxicity. Another relevant topic of the study in chapter 4 is the randomization of patients into two groups: one receiving vitamin supplementation and the other not. Mixed results and study designs are available for cancer prevention by vitamin B12 or folate supplementation (42, 43), and more recent studies show even an increased risk for lung or colorectal cancers by vitamin B12 supplementation (44, 45). To our knowledge there is no randomized evidence to support the use of folic acid or vitamin B12 in cancer treatment. Negative or neutral results from randomized trials, such as ours in chapter 4, can provide a counterbalance with reliable information to the popularity of vitamin use in cancer patients, which is often promoted without clinical evidence by social media (46-48).In the current landscape of increased treatment options and increasing drug costs patient selection for the right treatment is very important to avoid unnecessary exposure of patients to toxic treatments and to enhance efficient use of healthcare costs. As described above important biomarkers like HER2 and PD-1 have been developed but these biomarkers require invasive tumor tissue analysis. Circulating microRNAs (ci-miRNAs) are extensively studied as potential noninvasive biomarkers for different tumor types. The definite role of miRNAs in EC and GC is unclear (49-51) and limited data are available about the function of miRNAs in plasma of patients with EC and GC who are treated with palliative chemotherapy. Chapter 5 describes a study in which we investigated the prognostic and predictive value of ci-miRNAs measured by droplet digital PCR (ddPCR) within the plasma samples of patients treated with palliative chemotherapy for advanced EC or GC, as discussed in chapter 4. After conducting a literature search, miRNAs were chosen if evidence was reported in at least two independent publications. The selected miRNAs are as follows: for EAC and ESCC, miR-375, miR-200c-3p, miR-21-5p, and miR-148a-3p; for GC, miR-200c-3p, miR-141-3p, miR-146a-5p, and miR-218-5p. These ci-miRNAs were all known to be detectable in blood samples (52). A total of 225 plasma