85 [89Zr]Zr-DFO-durvalumab PET/CT before durvalumab treatment in R/M SCCHN patients and reported as the percentage injected dose (%ID/g). The optimal dose for [89Zr]Zr-DFOdurvalumab PET-imaging was determined based on pharmacokinetic blood analyses and visual and quantitative PET analyses. After dose finding, we aimed to include an additional 43 patients receiving the optimal dose [89Zr]Zr-DFO-durvalumab. However, the study was closed early for enrolment in December 2020 due to the registration of pembrolizumab as 1st line treatment for R/M SCCHN patients in the Netherlands (June 2020). In total, we enrolled an additional 19 patients who underwent the same procedures as described above, except for the collection of blood samples for pharmacokinetic analyses. Imaging assessment ceCT and/or MRI and [18F]FDG PET/CT Baseline ceCT/MRI and [18F]FDG PET/CT-scans were centrally reviewed by two independent radiology and nuclear medicine physicians (E.H.J.G.A., R.H.), according to standard clinical practice. The evaluation of CT lesions was performed according to RECIST 1.1 26. Lesion size was defined as the mean size in millimeters (mm) as determined by two reviewers. The [18F]FDG PET/CT-scans were assessed using the PET Response Criteria in Solid Tumors (PERCIST) criteria 27. A tumor lesion was defined visually positive based on anatomical substrate on low-dose CT in combination with higher than surrounding [18F]FDG-uptake, and a diameter on ceCT or MRI of ≥10mm or ≥15mm in lymph nodes 26. The maximum and peak standardized uptake values (SUV) based on body weight were obtained, as well as metabolic tumor volume (MTV) and total lesion glycolysis (TLG). [89Zr]Zr-DFO-durvalumab PET/CT The quantification of tumor lesions was performed by placing a 3D sphere in a [18F]FDG-positive lesions using Accurate tool software developed in IDL version 8.4 (Harris Geospatial Solutions, Bloomfield, USA)) 28. This was done for all [18F]FDG-positive lesions, irrespective of visual [89Zr] Zr-DFO-durvalumab uptake. This volume of interest (VOI) was manually delineated around the entire lesion if this could be distinguished from the background. In tumor lesions without evident visual zirconium-89 uptake, a spherical VOI of 1cm3 was drawn at the anatomical location of the tumor lesion, based on the low dose CT, diagnostic CT and [18F]FDG PET/CT. On a lesion level, the SUVpeak of individual lesions were determined to report tumor tracer-uptake. For healthy organs and blood pool, SUVmean was reported. To correct for variable concentrations of circulating [89Zr]Zr-DFO-durvalumab, tumor-to-blood (TTB) ratios were reported as SUVpeak tumor/ SUVmean blood. The blood pool activity was measured in a spherical VOI in the descending aorta. To correct for differences in number of lesions per patient, the lesional SUVpeak and [18F]FDG TLG values of one individual patient were summarized as geometric mean (gm) values. This was used to correlate tracer-accumulation to treatment response. Furthermore, to correct 5
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