Thyroid cancer is a rare cancer with an excellent prognosis with standard care (including surgery and radioactive iodine therapy). However, a minority may show progression to refractory status.... Show moreThyroid cancer is a rare cancer with an excellent prognosis with standard care (including surgery and radioactive iodine therapy). However, a minority may show progression to refractory status. These advanced radioactive iodine-refractory thyroid cancer patients often have an aggressive disease course and poor prognosis. Unfortunately, no good treatment options are available for these patients.The registered drugs for this purpose include molecularly targeted therapy with the tyrosine kinase inhibitors (TKIs) lenvatinib, sorafenib, and as second-line cabozantinib. These agents were shown to delay progressive disease in clinical trials, but not overall survival. Moreover, the setting of a clinical trial is often stricter than real-life, as reflected by less favorable outcomes in real-world data. Furthermore, these drugs frequently have (intolerable) adverse events. When the limited treatment options for refractory thyroid cancer have been exhausted, inclusion in clinical trials is often recommended by international guidelines.More recent ‘basket trials’ also study tumor type-agnostic prescription of drugs based on molecular tumor profiling; e.g. an ALK TKI in presence of an ALK gene fusion. The molecular characterization of neoplasms may also improve diagnosis and/or help direct the further management strategy; e.g. in indeterminate thyroid cytopathology, or in specific cases of Multi-UniFocality in contrast to multifocality. Show less
Krens, L.L.; Baas, J.M.; Guchelaar, H.J.; Gelderblom, H. 2018
The use of the epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab is limited to colorectal cancer (CRC) patients with KRAS wild type tumors and more recently in RAS wild... Show moreThe use of the epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab is limited to colorectal cancer (CRC) patients with KRAS wild type tumors and more recently in RAS wild type only. After having become chemotherapy refractory, treatment options are limited for this substantial patient group. This means that there is an urgent need to optimize anti-EGFR therapy. The work presented in this thesis aimed at optimising EGFR targeted monoclonal antibody therapy in metastatic CRC. This thesis investigates several strategies to refine EGFR targeted monoclonal antibody therapy in CRC by: 1. statins and their ability to phenoconvert KRAS mutant CRC; __ 2. exploration of polymorphisms in the gene encoding FCGR3A and their association __with cetuximab efficacy; __ 3. and investigating the pharmacokinetics of cetuximab and panitumumab in patients with renal or hepatic dysfunction. __ Show less
