1. Fizikalni modeli imunoterapije in radioterapijeDamijan Valentinuzzi, Martina Vrankar, Katja Uršič Valentinuzzi, Mojca Unk, Olga Gordeeva, Alen Hadžić, Gregor Serša, Maja Čemažar, Robert Jeraj, 2023, published scientific conference contribution Abstract: V prispevku bomo predstavili rezultate fizikalnih modelov imunoterapije, ki smo jih razvili v programski skupini Medicinska fizika na Fakulteti za matematiko in fiziko Univerze v Ljubljani. Glavni cilj raziskav je bila prepoznava bioloških značilnosti tumorjev, od katerih je odvisen odziv na zdravljenje s protitelesi receptorja programirane celične smrti l (angl. anti-programmed-death-1 (anti-PD-1)). Posebno pozornost smo namenili meritvam modelskih parametrov ter preverbi rezultatov modeliranja, kar je eden izmed predpogojev za uspešno translacijo modeliranja v rutinsko predklinično in klinično prakso. Predstavili bomo tudi načrte za prihodnost, tj. modeliranje kombinacije anti-PD-1 in radioterapije.
Keywords: imunoterapija, radioterapija, medicinska fizika, tumorji
Published in DiRROS: 16.06.2023; Views: 383; Downloads: 98
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2. Quantitative imaging biomarkers of immune-related adverse events in immune-checkpoint blockade-treated metastatic melanoma patients : a pilot studyNežka Hribernik, Daniel T. Huff, Andrej Studen, Katarina Zevnik, Žan Klaneček, Hamid Emamekhoo, Katja Škalič, Robert Jeraj, Martina Reberšek, 2022, original scientific article Abstract: Purpose: To develop quantitative molecular imaging biomarkers of immune-related adverse event (irAE) development in malignant melanoma (MM) patients receiving immune-checkpoint inhibitors (ICI) imaged with 18F-FDG PET/CT. Methods: 18F-FDG PET/CT images of 58 MM patients treated with anti-PD-1 or anti-CTLA-4 ICI were retrospectively analyzed for indication of irAE. Three target organs, most commonly affected by irAE, were considered: bowel, lung, and thyroid. Patient charts were reviewed to identify which patients experienced irAE, irAE grade, and time to irAE diagnosis. Target organs were segmented using a convolutional neural network (CNN), and novel quantitative imaging biomarkers - SUV percentiles (SUVX%) of 18F-FDG uptake within the target organs - were correlated with the clinical irAE status. Area under the receiver-operating characteristic curve (AUROC) was used to quantify irAE detection performance. Patients who did not experience irAE were used to establish normal ranges for target organ 18F-FDG uptake. Results: A total of 31% (18/58) patients experienced irAE in the three target organs: bowel (n=6), lung (n=5), and thyroid (n=9). Optimal percentiles for identifying irAE were bowel (SUV95%, AUROC=0.79), lung (SUV95%, AUROC=0.98), and thyroid (SUV75%, AUROC=0.88). Optimal cut-offs for irAE detection were bowel (SUV95%>2.7 g/mL), lung (SUV95%>1.7 g/mL), and thyroid (SUV75%>2.1 g/mL). Normal ranges (95% confidence interval) for the SUV percentiles in patients without irAE were bowel [1.74, 2.86 g/mL], lung [0.73, 1.46 g/mL], and thyroid [0.86, 1.99 g/mL]. Conclusions: Increased 18F-FDG uptake within irAE-affected organs provides predictive information about the development of irAE in MM patients receiving ICI and represents a potential quantitative imaging biomarker for irAE. Some irAE can be detected on 18F-FDG PET/CT well before clinical symptoms appear.
Keywords: melanoma, malignant melanoma, immune-checkpoint inhibitors, molecular imaging biomarkers
Published in DiRROS: 07.09.2022; Views: 509; Downloads: 148
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