Thesis

20 Chapter 1 In Part 1 of this thesis, the potential of detecting endometrial and ovarian cancer in patient-friendly samples is described. In Chapter 2, the feasibility of endometrial cancer detection in urine is evaluated by testing three methylation markers in different urine fractions. In Chapter 3, a systematic review of the literature is performed to select which methylation markers for endometrial cancer detection in patient-friendly sample types deserve further development. In Chapter 4, nine methylation markers, retrieved from Chapters 2 and 3, are tested for endometrial cancer detection in paired urine, cervicovaginal self-samples, and clinician-taken cervical scrapes to comprehensively determine and compare their performance in different patient-friendly sample types. In Chapter 5, the use of patient-friendly samples for ovarian cancer detection is explored using different molecular analyses. Nine methylation markers are analyzed in urine, cervicovaginal self-samples, and clinician-taken cervical scrapes. Additionally, copy number aberrations and cfDNA fragmentation patterns are analyzed in the urine of ovarian cancer patients. In Part 2 of this thesis, the applicability of urine for the detection of non-small cell lung cancer (NSCLC) is evaluated. In Chapter 6, three methylation markers are tested to explore the use of urine for the detection of non-metastatic primary and recurrent NSCLC. For successful clinical implementation, it is essential to explore the day-today and within-days variation in urine cfDNA measurements to fully comprehend its potential as a diagnostic tool. Therefore, in Chapter 7, the dynamics of methylated cfDNA in patients with advanced stage NSCLC are investigated to determine whether a preferred collection time and frequency exists. The outcomes of this thesis contribute to a new era of patient-friendly solutions for cancer detection that can be widely implemented in future clinical practice.

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