84 Chapter 5 MATERIALS AND METHODS Patients Eligible patients were aged ≥18 years, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a life expectancy of at least 12 weeks. Patients had histologically or cytologically confirmed R/M SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx not amenable to curative therapy, with no prior systemic treatment for R/M SCCHN. Patients with known leptomeningeal carcinomatosis, symptomatic or uncontrolled brain metastases requiring treatment, were excluded. Patient recruitment was performed in four university medical centers in the Netherlands (Radboudumc, UMC Groningen, Amsterdam UMC and Leiden UMC). The study was performed in accordance with the Declaration of Helsinki and approved by the institutional review board of each participating center. Procedures Contrast-enhanced (ce)CT and/or MRI, [18F]FDG PET/CT and [89Zr]Zr-DFO-durvalumab PET/CT At baseline, all patients underwent ceCT and/or MRI of the head and neck, chest and abdomen, combined with whole-body [18F]FDG PET/CT and [89Zr]Zr-DFO-durvalumab PET/CT. [18F]FDG PET/CT was performed according to European Association of Nuclear Medicine (EANM) guidelines version 1.0 20 and the 89Zr-imaging procedure was harmonized between participating EARL-accredited centers (PET/CT-systems) 21. Patients underwent [89Zr]Zr-DFO-durvalumab PET/CT 5 days after intravenous (IV) injection of ~37 MBq [89Zr]Zr-DFO-durvalumab. Details on, conjugation, radiolabeling and quality control of [89Zr]Zr-DFO-durvalumab and image acquisition and reconstruction are described in the supplements 21-24. After baseline imaging, all patients were planned for durvalumab treatment (fixed dose of 1500mg iv once every 4 weeks) starting within one week after PET-imaging until disease progression or unacceptable toxicity, for a maximum of 24 months. Data on adverse events was collected up to 90 days after the last treatment dose and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Treatment evaluation was performed with ceCT of the head and neck, chest and abdomen at baseline and every 8 weeks during treatment, using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Participants were contacted every 3 months to assess survival after discontinuation of durvalumab treatment. [89Zr]Zr-DFO-durvalumab PET/CT Dose finding Based on prior dose finding studies with 89Zr-labeled antibodies, we aimed to enroll a minimum of 3 patients per dose cohort (2, 10 or 50 mg durvalumab) 25. All patients received an intravenous injection of 2mg [89Zr]Zr-DFO-durvalumab. For the 10 and 50mg cohort, [89Zr]Zr-DFOdurvalumab was complemented with 8 and 48 mg unlabeled durvalumab, respectively. For pharmacokinetic purposes, blood plasma samples were drawn within 10 minutes after injection and five days later (day of the PET scan). Plasma radioactivity was measured in a gamma counter
RkJQdWJsaXNoZXIy MTk4NDMw