Dendritic cell immunotherapy versus bevacizumab plus irinotecan in recurrent malignant glioma patients: a survival gain analysis

Stefan-Alexandru Artene,1 Adina Turcu-Stiolica,2 Richard Hartley,1 Marius Eugen Ciurea,3 Oana Daianu,1 Corina Brindusa,1 Oana Alexandru,4 Ligia Gabriela Tataranu,5 Stefana Oana Purcaru,1 Anica Dricu1 1Unit of Biochemistry, 2Department of Biostatistics, 3Department of Plastic and Reconstructive Surgery, 4Department of Neurology, University of Medicine and Pharmacy of Craiova, Craiova, 5Department of Neurosurgery, “Bagdasar–Arseni” Emergency Hospital, Bucharest, Romania Background: The bevacizumab and irinotecan protocol is considered a standard treatment regimen for recurrent malignant glioma. Recent advances in immunotherapy have hinted that vaccination with dendritic cells could become an alternative salvage therapy for the treatment of recurrent malignant glioma.Methods: A search was performed on PubMed, Cochrane Library, Web of Science, ScienceDirect, and Embase in order to identify studies with patients receiving bevacizumab plus irinotecan or dendritic cell therapy for recurrent malignant gliomas. The data obtained from these studies were used to perform a systematic review and survival gain analysis.Results: Fourteen clinical studies with patients receiving either bevacizumab plus irinotecan or dendritic cell vaccination were identified. Seven studies followed patients that received bevacizumab plus irinotecan (302 patients) and seven studies included patients that received dendritic cell immunotherapy (80 patients). For the patients who received bevacizumab plus irinotecan, the mean reported median overall survival was 7.5 (95% confidence interval [CI] 4.84–10.16) months. For the patients who received dendritic cell immunotherapy, the mean reported median overall survival was 17.9 (95% CI 11.34–24.46) months. For irinotecan + bevacizumab group, the mean survival gain was -0.02±2.00, while that for the dendritic cell immunotherapy group was -0.01±4.54.Conclusion: For patients with recurrent malignant gliomas, dendritic cell immunotherapy treatment does not have a significantly different effect when compared with bevacizumab and irinotecan in terms of survival gain (P=0.535) and does not improve weighted survival gain (P=0.620). Keywords: malignant glioma, irinotecan, bevacizumab, dendritic cell, systematic analysi

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The term “shoulder formation” refers to an increase of the density decay length in the scrape-off layer (SOL) observed in many tokamaks during L-mode operation when a density threshold is reached. Recent experiments in ASDEX Upgrade (AUG) and JET have shown that the shoulder forms when the divertor collisionality in the divertor electrically disconnects filaments from the wall. This leads to a transition from the sheath limited to the inertial regime and to an enhancement of radial particle transport, in good agreement with analytical models. In the present work, the validity of such a mechanism is investigated in the more reactor-relevant H-mode regime. For this, a cold divertor H-mode scenario is developed in AUG using different levels of D puffing and N seeding, in which inter-ELM filaments and SOL density profiles are measured. The basic relation between filament size and divertor collisionality is still valid in H-mode plasmas, albeit an additional condition related to the gas fueling rate has been foundfor the formation of the shoulder.Peer reviewe