This dissertation focuses on developing new mathematical and statistical methods to properly represent time-varying covariates and model them within the context of time-to-event analysis. This... Show moreThis dissertation focuses on developing new mathematical and statistical methods to properly represent time-varying covariates and model them within the context of time-to-event analysis. This research topic is motivated by specific clinical questions aimed at gaining insights into personalised treatments for cardiological and oncological patients. The main purpose is to enrich the knowledge available for modelling patients’ survival with relevant features related to the time-varying processes of interest.The efforts of this work address the complexities of both (i) developing adequate dynamic characterizations of the processes under study (i.e., representation problem) and (ii) identifying and quantifying the association between time-varying processes and patient survival (i.e., time-to-event modelling problem). In both cases, the main issue is dealing with complex data sources while taking into account the nature of the processes and managing the complex trade-off between clinical interpretability and mathematical formulation.By solving the aforementioned statistical complexities, this work is not only impacting the community of researchers in mathematics and statistics. The development of these novel methodologies may represent a significant step forward in the definition of customized and flexible monitoring tools to support doctors and clinicians in their work.*********This doctoral dissertation was part of a cotutelle agreement between the Politecnico di Milano and Leiden University Show less
Gemcitabine was examined as switch maintenance therapy after standard first line chemotherapy in the NVALT19 trial, which provided the first conformation of gemcitabine activity in malignant... Show moreGemcitabine was examined as switch maintenance therapy after standard first line chemotherapy in the NVALT19 trial, which provided the first conformation of gemcitabine activity in malignant mesothelioma (MM). We describe additional analyses to confirm the prognostic value of CYFRA 21-1 and examine the prognostic value of CYFRA 21-1 in MM patients treated with gemcitabine. We also searched how gemcitabine could improve antitumor immune responses by positively modulating the immune system.In this thesis we describe a cohort of 107 malignant mesothelioma patients treated with nivolumab in the Netherlands. The real- world data of single agent PD-1 blocking were disappointing compared to previous reported single arm phase II trials. To examine clinical and peripheral blood biomarkers univariable and multivariable analyses were performed.As malignant peritoneal mesothelioma is even rarer then pleural mesothelioma, we hypothesized that centralization of care for peritoneal mesothelioma could benefit patients as they would likely receive treatment more often.Prognosis has a significant influence on the treatment preferences of patients, but prognosis of individual MM patients is variable and is hard to predict. We presented the MESOPRO score for patient with MM which are about the start with any systemic treatment. Show less
