Sarah Verhoeff

13 General introduction and outline of this thesis monotherapy pembrolizumab was granted FDA and EMA approval as 1st line treatment option in patients with R/M SCCHN >6 months after primary treatment with a high PD-L1 expression, and in combination with chemotherapy for patients with an intermediate PD-L1 expression8. The HPV status has also been correlated to ICI response, suggesting that patients with HPV+ tumors show a trend towards an improved overall survival with anti-PD-1 therapy38. Despite the advances made in the treatment options for R/M SCCHN patients, still only a small subset of R/M SCCHN patients benefit from ICI treatment. Selecting patients based on the PD-L1 CPS score has important limitations and subsequent consequences for a patient’s treatment options and associated survival chances. Molecular imaging might aid in the selection of patients for ICI treatment, for example by visualizing all accessible PD-(L)1 in a patient39. In this thesis, we report the results of the multi-center PINCH study on PD-L1 PET-imaging with 89Zr-labeled durvalumab in patients with advanced R/M SCCHN to predict durvalumab treatment response. The study design is illustrated in Figure 2. Figure 2. Molecular PET-imaging with 89Zr-labeled antibodies. A patient diagnosed with recurrent or metastatic SCCHN (1), receives an injection with 89Zr-labeled antibody (durvalumab) (2). Five days later, a PET/CT scan is performed (3). Afterwards, the patient initiated durvalumab treatment (4). Non-small cell lung cancer Lung cancer is the 1st and 2nd cause of cancer mortality in men (21.5%) and women (13.7%) in 202040. Most frequently, patients are diagnosed with non-small cell lung cancer (NSCLC) in an advanced stage41. Overall survival rates range from 59 months for patients with stage IA disease to four months for those with stage IV disease when untreated42,43. 1