Survival of patients with colorectal cancer improved markedly over the past decades, as a result of advances in screening, staging procedures, treatment, and surveillance. However, still about 20%... Show moreSurvival of patients with colorectal cancer improved markedly over the past decades, as a result of advances in screening, staging procedures, treatment, and surveillance. However, still about 20% of patients with colorectal cancer develop metachronous metastases and 20% of all patients with colorectal cancer have metastatic disease at diagnosis. Several treatment modalities, such as total mesorectal excision (TME) and preoperative (chemo)radiotherapy for rectal cancer, as well as adjuvant chemotherapy for stage III colon cancer, have been studied extensively and showed to improve cancer-related outcomes. On the contrary, the effectiveness of other treatment modalities including adjuvant chemotherapy for rectal cancer and for stage II colon cancer, and surgery of the primary tumour in incurable metastatic colorectal cancer are still subject of debate. Moreover, there is considerable short-term and long-term morbidity after (chemo)radiotherapy or surgery which should be taken into account. Further defining optimal treatment strategies is therefore of great importance. This thesis focused on improving evidence for treatment modalities that are currently subject of debate for patients with colorectal cancer. This was done using data from randomised controlled trials as well as cancer registry data. Show less
Colon cancer is the third most frequent malignancy in the Western world. Average 5 year-survival is around 70% and depends on the stage of the disease being very poor (under 10% 5-year survival)... Show moreColon cancer is the third most frequent malignancy in the Western world. Average 5 year-survival is around 70% and depends on the stage of the disease being very poor (under 10% 5-year survival) for stage IV patients and excellent (more than 90% 5 year survival) for stage I patients. The prognosis of patients with stage II varies between 80 and 60% 5-year survival. The causes of this variation remain unclear. Furthermore, the prognosis of patients with stage III has improved significantly, reaching 70% 5-year survival, since the introduction of adjuvant chemotherapy. However, still 30% of the patients with stage III disease that do not respond to chemotherapy. Therefore, reliable predictive and prognostic markers in stage II and III colon carcinoma are necessary to be able to elucidate whether a patient is going to respond to therapy or not and to be able to offer personalized treatment. In this research project, we aimed to identify predictive markers of therapy response in stage III disease and prognostic markers in stage II and III colon carcinoma. The first three chapters focus on the value of known single nucleotide polymorphisms (SNP) in genes involved in the activation, metabolism of chemotherapeutic drugs like 5-fluorouracil and oxaliplatin as well as in the repair of DNA damage caused by these drugs as predictive markers for therapy response. In the remaining chapters , the focus is placed on the identification of molecular prognostic markers in stages II and III. Several mutations in known cancer driver genes and genes involved in signal transduction have been studied. Show less
