Sarah Verhoeff

138 Chapter 8 SUMMARY In this thesis, we explored the potential of molecular PET imaging to optimize anti-cancer treatment strategies. In three clinical trials, we performed PET imaging with 89Zr-labeled antibodies in conjunction to conventional imaging with [18F]FDG PET/CT and contrast-enhanced CT, in patients with metastatic clear cell renal cell carcinoma, advanced head and neck cancer and earlystage non-small cell lung cancer. In these studies, we emphasized on diagnostic accuracy and the prognostic and predictive value of 89Zr-antibody PET. Part 1 Patients with metastatic clear cell renal cell carcinoma (mccRCC) show a heterogenous course of disease, from indolent to rapidly progressive disease without systemic treatment. MccRCC patients with a good or intermediate prognosis according to the International Metastatic RCC Database Consortium (IMDC) criteria, can be considered for a period of watchful waiting (WW). In the prospective cohort study IMPACT-RCC (NCT02228954) we studied the role of tumor metabolism and Carbonic Anhydrase IX (CAIX), as visualized by [18F]FDG and [89Zr]Zr-DFOgirentuximab PET/CT respectively, in predicting WW period. We enrolled 42 newly diagnosed mccRCC patients with a good or intermediate prognosis according to the IMDC criteria, considered eligible for a period of WW. In total 40 patients could be analyzed. In addition to conventional CT at the start of WW, [18F]FDG and [89Zr]Zr-DFO-girentuximab PET/CT resulted in the detection of more metastatic lesions (chapter 2). Those lesions were most frequently noticed in bone and soft tissue. In two patients, [89Zr]Zr-DFO-girentuximab PET/ CT detected new brain metastases warranting local treatment. [18F]FDG tumor uptake could improve the prediction of the WW period. Also in a subgroup of mccRCC patients with <2 IMDC risk factors and ≤2 involved organ sites (or “W&W criteria”) and associated favorable prognosis1, [18F]FDG PET/CT could improve the identification of patients with expected long period of WW. In chapter 3, we confirmed the favorable prognosis of patients meeting the W&W criteria. Low [18F]FDG uptake was associated with a prolonged WW period, independent of IMDC risk factors or involved organ sites. Moreover, patients with low [18F]FDG uptake (<3 SUVmax) or a negative PET/CT reported a WW duration of at least 12 months. In contrast, [89Zr]Zr-DFO-girentuximab PET/CT did not show prognostic value. Part 2 In the past decade, immune checkpoint inhibitors (ICI) targeting Programmed cell Death 1 or the Programmed cell Death Ligand 1 (PD-1 or PD-L1) have drastically changed the oncological landscape. Subsets of patients with metastatic disease showed impressive durable responses to ICI treatment. However, these response profiles challenges patient selection to increase the chance of effective treatment for the individual patient and to prevent unnecessary toxicity in