1. Early-time-point 18F-FDG-PET/CT and other prognostic biomarkers of survival in metastatic melanoma patients receiving immunotherapyNežka Hribernik, Katja Strašek, Andrej Studen, Katarina Zevnik, Katja Škalič, Robert Jeraj, Martina Reberšek, 2025, original scientific article Abstract: A considerable proportion of metastatic melanoma (mM) patients do not respond to immune checkpoint inhibitors (ICIs). There is a great need to develop noninvasive biomarkers to detect patients, who do not respond to ICIs early during the course of treatment. The aim of this study was to evaluate the role of early [18F]2fluoro- 2-deoxy-D-glucose PET/CT (18F-FDG PET/CT) at week four (W4) and other possible prognostic biomarkers of survival in mM patients receiving ICIs. Patients and methods. In this prospective noninterventional clinical study, mM patients receiving ICIs regularly underwent 18F-FDG PET/CT: at baseline, at W4 after ICI initiation, at week sixteen and every 16 weeks thereafter. The tumor response to ICIs at W4 was assessed via modified European Organisation for Research and Treatment of Cancer (EORTC) criteria. Patients with progressive metabolic disease (PMD) were classified into the no clinical benefit group (no-CB), and those with other response types were classified into the clinical benefit group (CB). The primary end point was survival analysis on the basis of the W4 18F-FDG PET/CT response. The secondary endpoints were survival analysis on the basis of LDH, the number of metastatic localizations, and immune-related adverse events (irAEs). Kaplan-Meier analysis and univariate Cox regression analysis were used to assess the impact on survival. Results. Overall, 71 patients were included. The median follow-up was 37.1 months (95% CI = 30.1–38.0). Three (4%) patients had only baseline scans due to rapid disease progression and death prior to W4 18F-FDG-PET/CT. Fifty-one (72%) patients were classified into the CB group, and 17 (24%) were classified into the no-CB group. There was a statistically significant difference in median overall survival (OS) between the CB group (median OS not reached [NR]; 95% CI = 17.8 months – NR) and the no-CB group (median OS 6.2 months; 95% CI = 4.6 months – NR; p = 0.003). Univariate Cox analysis showed HR of 0.4 (95% CI = 0.18 – 0.72; p = 0.004). median OS was also significantly longer in the group with normal serum LDH levels and the group with irAEs and cutaneous irAEs. Conclusions. Evaluation of mM patients with early 18F-FDG-PET/CT at W4, who were treated with ICIs, could serve as prognostic imaging biomarkers. Other recognized prognostic biomarkers were the serum LDH level and occurrence of cutaneous irAEs.
Keywords: melanoma, prognostic biomarkers, survival, immunotherapy
Published in DiRROS: 21.11.2025; Views: 445; Downloads: 169
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2. A half-century of nuclear research, education and training : Story of the JSI TRIGA reactorLuka Snoj, Klemen Ambrožič, L. Barbot, Ljudmila Benedik, Arne Bratkič, Ivana Capan, C. Reynard-Carette, Vladimir Cindro, Dušan Čalič, Christophe Destouches, B. Geslot, Alireza Haghighat, Romain Henry, Milena Horvat, Elchin Huseynov, Gregoire De Izzara, Radojko Jaćimović, Anže Jazbec, Igor Jenčič, Robert Jeraj, Malcolm Joyce, Domen Kotnik, Gregor Kramberger, Igor Lengar, Jan Malec, Igor Mandić, Valerio Mascolino, Vid Merljak, Marko Mikuž, Gilles Noguere, Julijan Peric, Anže Pungerčič, Vladimir Radulović, Sebastjan Rupnik, Borut Smodiš, Zdenka Šlejkovec, Marko Štrok, Žiga Štancar, Ingrid Švajger, N. Thiollay, Iztok Tiselj, Andrej Trkov, Bojan Žefran, Gašper Žerovnik, Ylenia Žiber, Tanja Goričanec, 2025, review article Abstract: The TRIGA Mark II research reactor at the Jožef Stefan Institute is a key facility in the field of nuclear research, characterized by its versatility and applicability in a wide range of scientific disciplines. This document highlights its operational history, contributions to nuclear safety, education and various scientific applications, including advances in reactor and radiation physics, neutron activation analysis, environmental science and even contributions to the fight against the COVID-19 pandemic. It highlights the reactor’s significant role in fostering international collaborations, improving computer modeling techniques for nuclear research, and providing invaluable educational experiences. The great versatility and applicability of the JSI TRIGA reactor is emphasized by its adaptability to various research needs and its ability to enable groundbreaking studies in both fundamental and applied sciences
Published in DiRROS: 11.04.2025; Views: 1085; Downloads: 329
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3. ▫$[^{18}\mathrm F]$▫FDG PET immunotherapy radiomics signature (iRADIOMICS) predicts response of non-small-cell lung cancer patients treated with pembrolizumabDamijan Valentinuzzi, Martina Vrankar, Nina Boc, Valentina Ahac, Žiga Zupančič, Mojca Unk, Katja Škalič, Ivana Žagar, Andrej Studen, Urban Simončič, Jens C. Eickhoff, Robert Jeraj, 2020, original scientific article Keywords: medical physics, medical imaging, oncology
Published in DiRROS: 15.07.2024; Views: 1080; Downloads: 436
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4. Prepoznavanje ogroženosti za nastanek raka dojk na mamografskih slikahŽan Klaneček, Andrej Studen, Katja Jarm, Mateja Krajc, Miloš Vrhovec, Robert Jeraj, 2024, published professional conference contribution Abstract: Za prehod s populacijskega na personalizirano presejanje za raka dojk je v prvi vrsti potrebno natančno prepoznavanje ogroženosti za razvoj raka dojk. Standardni modeli, ki temeljijo na klasičnih značilkah, niso najbolj zanesljivi. Z razvojem umetne inteligence, predvsem na področju globokega učenja, se je izkazalo, da modeli, ki so naučeni na mamografskih slikah, dosegajo signifikantno boljše rezultate pri napovedovanju ogroženosti. Trenutno je najboljši model za napovedovanje ogroženosti MIRAI, ki je bil uspešno validiran na različnih populacijah. A vendar so rezultati še daleč od popolnih in možnosti za izboljšave je ogromno, predvsem na področju razširitve uporabnosti modela za različne proizvajalce mamografskih aparatov, vključevanja longitudinalnih sprememb in uporabe segmentiranih slik dojke.
Keywords: obvladovanje raka, presejalni programi, rak dojk, mamografija
Published in DiRROS: 06.06.2024; Views: 1412; Downloads: 515
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5. 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: 1795; Downloads: 528
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6. 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: 1918; Downloads: 660
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