Maarten van der Doelen

General introduction and outline of the thesis

radium-223 therapy. One may also argue that radium-223 may be beneficial in patients with bone metastatic disease not yet being symptomatic, but having radiographic signs of bone-progression. (55) For PSMA-targeted RLT, selection criteria are disease progression on registered mCRPC therapies, sufficient expression of PSMA in all metastatic lesions on a pretherapeutic PSMA-ligand positron emission tomography (PET) scan, and adequate bone marrow and kidney function. (57) However, genotypic and phenotypic characteristics, such as histological PSMA expression or DNA damage repair alterations, might also be important selection criteria. OUTLINE OF THE THESIS The aim of this thesis was to evaluate radium-223 therapy and 225 Ac-PSMA RLT in mCRPC in daily clinical practice, with a focus on effect evaluation and the identification of prognostic parameters, in order to optimize patient selection for these therapies in the future. Part I of this thesis focuses on the effect evaluation of radium-223 therapy and 225 Ac PSMA RLT in mCRPC patients. In chapter 2 , we describe the findings of an observational cohort study which evaluated the efficacy, impact on quality of life and safety of 225 Ac-PSMA RLT in advanced mCRPC patients. Furthermore, this study explored predictive biomarkers on pretherapeutic tissue biopsies. In chapter 3 , we evaluate the immunological changes in mCRPC patients by phenotyping their peripheral blood mononuclear cells before, during, and after treatment with radium-223. In chapter 4 , we present the outcomes of a prospective Dutch multicenter study on health-related quality of life, psychological distress and fatigue in mCRPC patients who were treated with radium-223 therapy. Part II of this thesis describes studies that used real-world data to explore prognostic parameters in mCRPC patients treated with radium-223 therapy. In chapter 5, we describe the outcomes of a retrospective cohort study which aimed to identify pretherapeutic parameters that predict overall survival and treatment completion in mCRPC patients who were treated with radium-223 therapy in an academic care setting. The aim of the multicenter retrospective cohort study described in chapter 6 was to investigate whether ALP dynamics after the first radium-223 injection can act as

1

17