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Background: Treatment with programmed cell death receptor (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors is a promising strategy to lift tumour-induced immune response suppression. However, the current systemic treatment often causes autoimmune side effects. In more than 50% of squamous cell cervical cancer, PD-L1 expression is detected. Moreover, we observed high and interrelated rates of PD-L1 positive macrophages and regulatory T cells in metastatic lymph nodes of cervical cancer patients. As cervical cancer in general initially metastasizes to regional lymph nodes, local administration of durvalumab (a PD-L1 checkpoint inhibitor) at an early stage will deliver these antibodies exactly where they are needed, facilitating immune protection. This may result in a clinical benefit while reducing undesirable side effects.Methods: DURVIT is a non-randomized, single-arm, open-label, phase I study. Three escalating dose levels of intratumourally (i.t.) injected durvalumab will be tested, i.e. 5, 10 and 20 mg (three patients per dose level, with an additional three at the highest tolerated dose). The primary endpoint of this phase-I study is safety. Immune monitoring will consist of flow cytometric, immunohistochemical and functional T cell reactivity testing. The first patient has been included in this trial in November 2017.Discussion: Evidence of safety and biological efficacy of this locally administered checkpoint blockade may expand adjuvant therapy options for cervical cancer patients. Early metastatic spread of cervical cancer cells may thus be controlled in the draining lymph node basin, and beyond, and hopefully delay or even prevent the onset of disease recurrence.Trial Registration: NTR6119 , 1-nov-2016. [ABSTRACT FROM AUTHOR]

Background: [ 18 F]FDG-PET/CT is used for staging and treatment planning in patients with locally advanced cervical cancer (LACC). We studied if a PET-based prediction model could provide additional risk stratification beyond International Federation of Gynaecology and Obstetrics (FIGO) staging in our population with LACC to aid treatment decision making., Methods: In total, 183 patients with LACC treated with chemoradiation between 2013 and 2018 were included. Patients were treated according to FIGO 2009 and retrospectively reclassified according to FIGO 2018 staging system. After validation of an existing PET-based prediction model, the predicted recurrent free survival (RFS), disease specific survival (DSS) and overall survival (OS) at 1, 3, and 5 years, based on metabolic tumor volume (MTV), maximum standardized uptake value (SUV max ) and highest level of [ 18 F]FDG-positive node was calculated. Then the observed survival was compared to the predicted survival. An area under the curve (AUC) close to or higher than 0.7 was considered adequate for accurate prediction. The Youden (J) index defined survival chance cutoff values for low and high risk groups., Results: All AUC values for the comparison between predicted and observed outcomes were > 0.7 except for 5-year RFS and for 5-year OS which were close to 0.7 (0.684 and 0.650 respectively). Cutoff values for low and high risk survival chance were 0.44 for the 3-year RFS and 0.47 for the 5-year OS. The FIGO 2009 system could not differentiate between the risk profiles. After reclassification according to FIGO 2018, all patients with stage IIIC2 and IVB fell in the high risk and almost all patients with stages IB2-IIIB and IVA in the low risk group. In patients with stage IIIC1 disease the FIGO stage cannot discriminate between the risk profiles., Conclusions: Low and high risk patients with LACC can be identified with the PET-based prediction model. In particular patients with stage IIIC1 need additional risk stratification besides the FIGO 2018 staging. The Kidd model could be a useful tool to aid treatment decision making in these patients. Our results also support the choice of [ 18 F]FDG-PET/CT imaging in patients with LACC., (© 2024. The Author(s).)