Sarah Verhoeff

14 Chapter 1 Patients with early-stage NSCLC up to stage IIIA are considered for surgical resection or stereotactic radiotherapy (stage I) with curative intent. After radical surgical resection, the 5-year survival is best in patient with stage I disease and limited for patients with stage II disease with nodal involvement (N1) (60-80% vs. 35-45%, respectively)44,45. Subsequently, patients with N1 and N2 disease (Stage IIA and IIIA) may benefit from adjuvant chemotherapy, which results in an overall 4-5% absolute 5-years survival improvement46,47. In more advanced stages with no curative treatment options, the introduction of immune checkpoint inhibitors has improved survival significantly. Pembrolizumab has been registered for stage IV NSCLC with a PD-L1 expression of ≥50% of tumor cells and no EGFR mutation or ALK translocation, based on a PFS of 10.3 vs. 6.0 months compared to chemotherapy (p<0.001)48. Also, durvalumab was granted FDA and EMA approval for stage III disease as consolidation treatment after chemoradiation49. These promising results have suggested the benefit of ICI in earlier disease stage. The first publication of neo-adjuvant ICI in NSCLC patients are encouraging, with no important safety issues and major pathological response in 45% of the resected tumors50. In this thesis, we display the results of the PINNACLE study that focused on PD-L1 PET-imaging with [89Zr]Zr-DFO-avelumab (anti-PD-L1) in patients with resectable early-stage NSCLC and irresectable metastatic NSCLC to predict (pathological) response to avelumab treatment.