New systemic treatments, such as immunotherapy, have led to a huge improvement in the prognosis of some of the deadliest cancers in the past decade. A large proportion of patients, however, still does not respond to treatment. Biomarkers can help to guide treatment choices with the objective to optimize treatment outcome and minimize the adverse effects. In this thesis, several biomarkers are explored in melanoma and rectal cancer. In a systemic review, 18F-FDG PET/CT emerged as the most accurate imaging modality for detection of melanoma metastases, which is important for proper treatment selection in metastatic melanoma. For reevaluation of locally advanced rectal cancer after preoperative chemoradiotherapy, a CT scan of chest and abdomen showed added value for detection of new distant metastases. For the purpose of BRAF mutation analysis in rapidly progressive melanoma, three rapid mutation tests were compared to each other. In this setting, the Idylla BRAF-Mutation Test proved most suitable. Serum S100B and the occurrence of adverse events were studied as biomarkers during treatment with immunotherapy in melanoma. High-grade adverse events (grade 3 or 4) were associated with better objective responses, progression free survival and overall survival on treatment with the PD-1 inhibitor pembrolizumab. Early serum S100B changes (week 6), however, were not able to predict sustained responses to CTLA-4 and PD-1 inhibitors. Furthermore, this thesis showed that long-term survival can be achieved in metastatic melanoma with intestinal metastases and primary metastatic rectal cancer by multidisciplinary management and proper use of biomarkers.
|Kwalificatie||Doctor of Philosophy|
|Datum van toekenning||31-mrt-2021|
|Plaats van publicatie||[Groningen]|
|Status||Published - 2021|