[18F]FET PET-Guided management of pseudoprogression in glioblastoma (FET POPPING): the study protocol for a diagnostic randomized clinical trial.

Abstract

BACKGROUND: During follow-up of glioblastoma patients after chemoradiation, expert teams often observe abnormalities on MRI with difficulty in distinguishing between tumor growth and pseudoprogression. Although advanced MRI techniques such as perfusion weighted imaging provide additional information, diagnostic uncertainty often remains, leading to incorrect or delayed diagnosis, and inappropriate treatment, such as unnecessary surgery. [ 18F]Fluoro-ethyl-tyrosine positron emission tomography (FET PET) has good discriminating power for this setting. Still, this diagnostic tool is not used frequently in The Netherlands due to costs, logistics and uncertainty about clinical benefit. In the FET POPPING study, we aim to determine the added value of [ 18F]FET PET for clinical management of glioblastoma patients. METHODS: A multicenter diagnostic randomized clinical trial will be performed, from August 2024 until December 2027. Adult patients (n=144) with isocitrate dehydrogenase (IDH)-wildtype glioblastoma will be included, who, at least ≥3 months after the concomitant phase of standard temozolomide-based chemoradiation, have new or increased contrast enhancement on MRI, causing doubt between tumor growth or pseudoprogression. In this trial, pseudoprogression will be used as an encompassing term that includes radionecrosis and other treatment-related changes after (chemo-)radiotherapy. Included patients will be randomized 1:1 in two arms. The investigational arm receives an additional [ 18F]FET PET scan, and clinical management is based on the index MRI and [ 18F]FET PET together. Clinical management of the control arm is based on the index MRI alone. Exact clinical management, as based on the available imaging, is chosen at the discretion of the local multidisciplinary board. The primary study endpoints are (a) the percentage of patients undergoing unnecessary interventions and (b) health-related quality of life after 12 weeks. Secondary endpoints include time-to-diagnosis, overall survival, and cost-effectiveness. DISCUSSION: We hypothesize that the clinical management guided by an additional [ 18F]FET PET scan leads to fewer unnecessary interventions, better health-related quality of life after 12 weeks and among others reduced net healthcare costs, compared with management based on MRI only. TRIAL REGISTRATION: The trial is registered on ClinicalTrials.gov on the 24th of June 2024, with registration number NCT06480721.