Sarah Verhoeff

12 Chapter 1 as initial treatment strategy to delay unnecessary treatment toxicity, preserve or improve the quality of life and limit treatment costs. To improve the identification of mccRCC patients with indolent disease eligible for WW, molecular PET imaging could play an important role. The conventional work-up of a patient suspected for mccRCC consists of a contrast-enhanced CT of the thorax and abdomen, and sometimes of the head and neck region. Currently, the [18F]FDG PET/CT has no place as a diagnostic tool in this work-up. However, previous studies have shown that high [18F]FDG-uptake could identify mccRCC patients with a poor prognosis26,27. The characteristic over-expression of Carbonic anhydrase IX (CAIX) because of a mutational loss of Von Hippel Lindau protein, makes CAIX a suitable target for molecular PET-imaging in mccRCC patients. Previous imaging studies with radiolabeled girentuximab, a humanized monoclonal antibody targeting CAIX, have confirmed the potential of this antibody for the visualization of the primary tumor and metastatic ccRCC lesions28-30. In this thesis, we report the results from the IMPACT-RCC study, which assessed the value of [18F]FDG PET/CT and [89Zr]Zr-girentuximab PET/CT in predicting the duration of WW among mccRCC patients with a good or intermediate prognosis according to the IMDC criteria. Head and neck cancer Most cancers of the head and neck derive from the mucosal epithelium in the oral cavity, oropharynx, hypopharynx and larynx, and are collectively known as squamous cell carcinoma of the head and neck (SCCHN). SCCHN is the sixth most common cancer worldwide31. Cancer of the oral cavity, hypopharynx and larynx is generally associated with tobacco consumption, alcohol abuse or both. On the contrary, cancer of the oropharynx is increasingly attributed to an infection with human papillomavirus (HPV), requiring a different treatment strategy with an associated increased survival compared to HPV negative tumors of the head and neck32. Depended on the location and the extent of disease, the treatment of patients with locoregional HPV-/ HPV+ SCCHN consists of surgical resection with or without (chemo)radiation or chemoradiation only. Among patients with recurrent or metastatic disease, some are offered salvage resection or re-irradiation with curative intent33. The remaining patients generally have a poor prognosis34. Until recently, the first-choice palliative systemic treatment consisted of platinum chemotherapy (cisplatin/carboplatin) and 5-fluorouracil, in combination with cetuximab (epidermal growth factor receptor (EGFR) antibody). This intensive scheme results in a median overall survival is only 10.1 months, at the cost of potential high-grade toxicity and health related quality of life35,36. Therefore, there is a great need to optimize treatment approach in R/M SCCHN. Clinical trials evaluating the efficacy nivolumab (anti-PD-1) in in R/M SCCHN patients with disease progression within 6 months after platinum-based chemotherapy, have reported 1-year survival rates of 36.0% (28.5-43.4) compared to 16.6% (8.6-26.8) patients receiving a salvage chemotherapy regimen (HR 0.70 (97.73%CI 0.51-0.96, p=0.01)37. Patients with PD-L1 positive tumors compared to PD-L1 low/negative tumors, showed higher response rates and prolonged survival. As a result,