Sarah Verhoeff

11 General introduction and outline of this thesis normal-tissue accumulation and tumor accessibility of radiolabeled therapeutic monoclonal antibodies18. In this way, molecular imaging with radiolabeled antibodies can help to understand the working mechanism of new drugs and to potentially identify responders and non-responders before start of treatment19. Treatment perspectives for patients with solid tumors are changing rapidly. This thesis will focus on metastatic clear cell renal cell carcinoma (mccRCC), squamous cell carcinoma of the head and neck (SCCHN) and non-small cell lung cancer (NSCLC). Metastatic clear cell renal cell carcinoma Renal cell carcinoma (RCC) is the 7th most common type of cancer. Seventy percent of all RCCS have a clear cell component. About one third of the patients with RCC develop metastases, most frequently in the lung, bones, lymph node and the adrenal gland. The overall prognosis of mccRCC patients is highly variable, with a median overall survival ranging from 5 to 30 months7. In recent years, the prognosis has improved with the arrival immune checkpoint inhibitors (ICI). Before their introduction, first-line treatment consisted of monotherapy anti-angiogenic therapy targeted against VEGF or its receptor, e.g., bevacizumab, sunitinib or pazopanib20-22. Recent studies have shown improved survival rates of combination strategies (e.g., ipilimumab and nivolumab or pembrolizumab and axitinib) compared to sunitinib monotherapy, altering the standard first line treatment approach in mccRCC patients23,24. Upon diagnosis, patients with metastatic ccRCC are classified into good, intermediate and poor prognosis groups based on clinical parameters also known as the International Metastatic RCC Database Consortium (IMDC) Risk score7 (Table 1). Table 1. IMDC Criteria25 Karnofsky performance status <80% Time from diagnosis to systemic treatment <1 year Hb <LLN Corrected calcium >ULN Neutrophils >ULN Platelets >ULN Number of criteria Group Median overall survival 0 Favorable 43.2 months (95%CI 31.4-50.1) 1-2 Intermediate 33.5 months (95% CI 18.7-25.1) 3-6 Poor 7.8 months (95% CI 6.5-9.7) LLN= lower limit of normal; ULN= upper limit of normal Patients with rapid progressive disease at presentation need to start systemic treatment immediately. Among patients with a good or intermediate prognosis, a subgroup demonstrates indolent course of disease. In those patients, a period of watchful waiting (WW) can be considered 1