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Res. Pract."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Olfactory impairment is common in glioblastoma and has been associated with unfavorable overall survival. However, prior studies were limited by imbalances in key prognostic factors and the absence of longitudinal olfactory assessments to evaluate treatment-related neurotoxicity. The aim of the study is to determine whether olfactory function serves as an independent prognostic marker for survival, neurocognitive outcomes, and quality of life in glioblastoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Prospective, multicenter cohort study enrolling 64 glioblastoma patients and 64 matched healthy controls. Patients are stratified by extent of resection, O6-Methylguanine-DNA Methyltransferase promoter methylation, radiographic involvement of olfactory regions, baseline olfactory status, age, and Karnofsky performance status. Olfactory function is assessed serially using Sniffin\u2019 Sticks (identification and threshold tests) from diagnosis through treatment. Coronal T2- and T1-weighted MRI scans are reviewed independently by two blinded neuroradiologists to detect olfactory region involvement. Neurocognitive testing, psychosocial screening, and quality of life assessments are conducted at defined intervals. Next-generation sequencing from tumor tissue is employed to explore molecular underpinnings of hyposmia. Blood samples are collected in every study visit for potential parallel translational studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Perspective<\/jats:title>\n                    <jats:p>This is the first longitudinal study evaluating olfactory function as a prognostic biomarker in glioblastoma. Findings may inform risk stratification, guide neuroprotective strategies, and improve survivorship care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov, NCT06954636, date of registration 04-16-2025 (retrospectively registered);\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT06954636?cond=glioblastoma&amp;intr=olfactory&amp;rank=1\" ext-link-type=\"uri\">https:\/\/clinicaltrials.gov\/study\/NCT06954636?cond=glioblastoma&amp;intr=olfactory&amp;rank=1<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  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He received honoria by Horizon and Novocure. He has received a Clinician Scientist Stipend of the University Medicine Essen Clinician Scientist Academy (UMEA) sponsored by the faculty of medicine and Deutsche Forschungsgemeinschaft (DFG). Teresa Schmidt received honoraria and travel support from Novocure. Thomas Hummel did research together with and received funding from Sony, Tokyo, Japan; Smell and Taste Lab, Geneva, Switzerland; Takasago, Paris, France; Baia Foods, Madrid, Spain; Frequency Therapeutics, Farmington, CT, USA; Burghart, Holm, Germany. Bj\u00f6rn Scheffler is supported by the German Cancer Consortium (DKTK). Michael M\u00fcther received honoraria and travel support from Medac and ITM. Ken Herrmann reported receiving consultant fees from Advanced Accelerator Applications, a Novartis company, Amgen, AstraZeneca, Bain Capital, Bayer, Boston Scientific, Convergent, Curium, Debiopharm, EcoR1, Fusion, GE Healthcare, Immedica, Isotopen Technologien M\u00fcnchen, Janssen, Merck, Molecular Partners, NVision, POINT Biopharma, Pfizer, Radiopharm Theranostics, Rhine Pharma, Siemens Healthineers, Sofie Biosciences, Telix, and Theragnostics, ymabs, receiving research grants from Advanced Accelerator Applications, a Novartis company, Boston Scientific, Janssen, having stock or other ownership interests with AdvanCell, Aktis Oncology, Convergent, NVision, Pharma 15, and Sofie Biosciences. Martin Glas has received research grants from Novocure. He has received honoraria from Roche, Seagan, Servier,\u00a0Novartis, UCB, Abbvie, Daiichi Sankyo, Bayer, Janssen-Cilag, Kyowa Kirin, Medac, Cecava, CeGaT, Merck and Novocure. He has received travel support from Novocure and Medac. Sied Kebir received honoraria and travel support from Novocure. He has received research support from Servier. No other potential conflicts of interest relevant to this article exist.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"51"}}