18 Chapter 1 out cancer. Biomarker testing in patient-friendly material could aid the triage of women presenting with postmenopausal blood loss, guide screening for primary endometrial cancer in high-risk women, and help monitor for recurrent endometrial cancer. 1.5.2 Ovarian cancer Ovarian cancer is the most deadly gynecological cancer worldwide, with 314,000 new diagnoses and over 207,000 deaths in 2020 (75). This cancer is known as a ‘silent killer’ as it often remains unnoticed until the disease has reached an advanced and incurable stage. Women with germline mutations like Lynch syndrome and BRCA1/2 have an increased lifetime risk of ovarian cancer (81). While endometrial cancers are mostly low-grade, the majority of ovarian cancers are high-grade. The most common histological subtype of ovarian cancer (~70-80%) is epithelial high-grade serous ovarian cancer, which is believed to originate from the fallopian tube (82). Women typically present with late-stage ovarian cancer when prognosis is poor and there are currently no effective screening or early detection methods (83). Pre-operative risk assessment to determine whether an ovarian mass is benign or (pre)malignant consists of radiographic imaging of the ovarian mass and a serum CA-125 measurement. The preoperative differentiation between benign and malignant ovarian masses is challenging using current diagnostic methods. More accurate methods are warranted to detect ovarian cancer early and to preoperatively differentiate between benign and malignant ovarian masses to streamline specialist referral. 1.5.3 Lung cancer Lung cancer accounts for the highest mortality rate globally, with an estimated number of 1,8 million deaths in 2020 (75). The majority of lung cancer cases are associated with tobacco use. Lung cancer originates from the cells of the respiratory epithelium and is divided into two main subtypes, small cell lung cancer (~15% of cases) and non-small cell lung cancer (NSCLC; ~85% of cases) (84). Despite advancements in the therapeutic landscape of NSCLC, mortality rates remain high. The majority of advanced NSCLC patients lack oncogenic alterations suitable for targeted treatment and only a minority of patients (~20%) respond to immunotherapy (85). With stage at diagnosis as most important prognostic factor, early detection is critical for treatment with curative intent. Therefore, large screening trials were initiated to address the value of low-dose computed tomography (LDCT) for lung cancer detection in high-risk groups (86-89). Although effective in detecting lung cancer at an earlier stage, a high number of false positives (96%) was observed resulting in unnecessary diagnostic work-up and loss of cost-effectiveness (89). Novel diagnostic tools are needed to manage positive LDCT screening outcomes and decrease false positive rates.
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