{
  "abstract": "Introduction Treatment with bevacizumab achieves both tumour stabilisation or regression and preservation or improvement of hearing. However, the efficacy of bevacizumab varies between patients and within patients. Side effects due to bevacizumab treatment are also common. It would be of value to predict therapeutic response prior to initiating therapy to prevent unnecessary exposure in patients unlikely to benefit.Methods and analysis We aim to recruit 25 patients with NF2-related schwannomatosis (NF2) with bilateral vestibular schwannomas. Patients will receive an intravenous injection of 37 MBq [89Zr]bevacizumab followed by positron emission tomography (PET)/CT imaging 4 days later. After clinical evaluation at baseline, patients undergo bevacizumab treatment and are followed up at 3 and 6 months. The primary objective is to examine associations between pretreatment [89Zr]bevacizumab uptake on PET/CT and changes in multiple hearing outcomes and radiological characteristics of the target tumour following treatment. Secondary outcome measures include vestibular functioning, patient reported outcome measures, cranial nerve functionality, peripheral neurology, non-target schwannoma response and renal function. Given the explorative nature of the study, associations between PET-derived metrics and clinical and radiological outcomes will be examined without formal hypothesis testing, using generalised estimating equations to account for within-patient correlation. Pairwise associations will be summarised in an association matrix with multiplicity addressed using an all-resolutions inference approach, and findings will be considered hypothesis generating.Ethics and dissemination This study was submitted via the Clinical Trials Information System reviewed and approved by the Medical Research Ethics Committee Leiden–The Hague–Delft Delft. The study findings will be disseminated through publication in peer-reviewed scientific journals and by presentation at national and international conferences.Trial registration number The trial is registered at ClinicalTrials.gov Protocol Registration and Results System under the registration ID: NCT05685836.",
  "authors": [
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Jules P J Douwes"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Annemijn L Tops"
    },
    {
      "affiliations": [
        "Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Petra Dibbets-Schneider"
    },
    {
      "affiliations": [
        "Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Berit M Verbist"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Constanza A Fuentealba Bassaletti"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Jeroen C Jansen"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Kim S Koetsier"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, Erasmus MC, Rotterdam, The Netherlands"
      ],
      "name": "Victor S van Dam"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Radboud W Koot"
    },
    {
      "affiliations": [
        "Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Floris H P van Velden"
    },
    {
      "affiliations": [
        "Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Martin Pool"
    },
    {
      "affiliations": [
        "Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centres, Amsterdam, The Netherlands"
      ],
      "name": "Daniëlle Vugts"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Josefine E Schopman"
    },
    {
      "affiliations": [
        "Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Jelle J Goeman"
    },
    {
      "affiliations": [
        "Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands",
        "Biomedical Photonic Imaging Group, University of Twente Faculty of Science and Technology, Enschede, The Netherlands",
        "Department of Radiation Science and Technology, Faculty of Science and Technology, Delft University of Technology, Delft, The Netherlands"
      ],
      "name": "Lioe-Fee De Geus-Oei"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology-Head and Neck Surgery, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Erik F Hensen"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Hans A Gelderblom"
    }
  ],
  "title": "[89Zr]bevacizumab PET/CT imaging of vestibular schwannomas for the prediction of bevacizumab treatment effect in patients with symptomatic NF2-related schwannomatosis: a study protocol for a phase II single centre, prospective, feasibility trial",
  "uid": "7c16e1dc-1eab-51f7-a58b-0af56ec88b81"
}