Florian Rosar

Large language models (LLMs) are increasingly explored for clinical use. However, the extent to which such models can reliably support physicians in reporting, staging, and the assessment of classification remains an active area of research. This study aimed to evaluate and compare multiple LLMs for automated PROMISE V2 classification for prostate cancer. A total of 126 unambiguous German-language PSMA PET/CT text reports were retrospectively analyzed, with reference standards established by expert consensus based on image interpretation and the original report text. Five LLMs (GPT-5.4, DeepSeek-V3.2, Claude Sonnet 4.6, Gemini 3 Flash and Grok 4) were assessed using two English-language prompting strategies of varying complexity. Agreement with the reference standard served as the primary endpoint. Performance varied in the short-prompt setting (36.5–79.4%) but improved consistently with the long prompt (74.6–86.5%), with Gemini 3 Flash achieving the highest agreement. Across PROMISE V2 subcategories, agreement rates were high (miT: 81.0–92.1%, miN: 92.9–96.0%, miM: 92.9–95.2%), despite inter-model differences. In conclusion, contemporary LLMs demonstrate promising performance in deriving PROMISE V2 scores from unambiguous original report texts, particularly when guided by detailed prompts.

Purpose: PSMA RLT employing ¹⁷⁷ Lu by use of [ ¹⁷⁷ Lu]Lu-PSMA-617 has been demonstrated to be effective and well-tolerated, maintaining or even improving quality of life. Other radionuclides such as ¹⁶¹ Tb are currently under investigation concerning clinical feasibility and therapeutic efficacy. However, patient-centered evaluations of well-being and adverse events are scarce. This study evaluates the impact of [ ¹⁶¹ Tb]Tb-PSMA-617 RLT on health-related quality of life (HRQoL) across multiple scales, including adverse events. Methods: Analysis included 20 advanced, heavily pre-treated mCRPC patients enrolled in the REALITY registry (NCT04833517) who received [ ¹⁶¹ Tb]Tb-PSMA-617 RLT (median two cycles; mean activity per cycle: 6.1 ± 1.2 GBq) after prior conventional PSMA RLT. HRQoL, covering physical, emotional, cognitive, and social functioning, was assessed using EORTC QLQ-C30. Hematotoxicities, liver and kidney function impairments, as well as xerostomia were evaluated according to CTCAE v5.0. For statistical analysis, the Wilcoxon matched-pairs signed-rank test was employed, with a significance threshold set at p < 0.05. Results: Analysis of QLQ-C30 demonstrated that patient-reported well-being was largely maintained. Increased tiredness reached statistical significance ( p = 0.036). Global health ( p = 0.581) and overall quality of life ( p > 0.999) remained stable throughout therapy. Most CTCAE ratings were mild or moderate. Worsening under therapy was limited: One anemia case progressed from CTCAE °2 to °4, and another from °2 to °3. Regarding renal function, two cases progressed from °2 to °3. No cases of xerostomia higher than °2 were observed. Conclusion: [ ¹⁶¹ Tb]Tb-PSMA-617 RLT represents a well-tolerated and safe treatment option for advanced mCRPC, with patient-reported quality of life maintained over time, with only rare higher-grade hematological and renal toxicities.

Background: Despite its high diagnostic accuracy, conventional prostate-specific membrane antigen (PSMA) targeting positron emission tomography/computed tomography (PET/CT) fails to localize disease in a non-negligible proportion of patients with biochemical recurrence (BCR). Preliminary studies in small patient cohorts suggest that [ ⁸⁹ Zr]Zr-PSMA-617 PET/CT may improve localization of BCR, presumably due to its longer physical half-life, in patients with previously failed localization efforts. This study seeks to validate reported preliminary detection rates in a markedly larger cohort and to identify predictive biomarkers for positive findings on [ ⁸⁹ Zr]Zr-PSMA-617 PET/CT in patients with prior negative conventional PSMA PET/CT. Results: Among 70 patients with prior negative conventional PSMA PET/CT, 52 demonstrated tumor suspicious lesions on subsequent [ ⁸⁹ Zr]Zr-PSMA-617 imaging, resulting in a detection rate of 74.3%. A total of 76 lesions were detected, predominantly in lymph nodes (46.1%) and local recurrence sites (40.8%), with fewer osseous (9.2%) and visceral (4.0%) metastases. Scan positivity was significantly higher in patients with higher prostate-specific antigen levels (PSA > 0.2 ng/mL, p = 0.002) and lower PSA doubling times (PSA dt < 4 months, p = 0.041). Conclusion: In the largest cohort to date investigating PET/CT with long-lived PSMA tracers, [ ⁸⁹ Zr]Zr-PSMA-617 PET/CT demonstrated a high detection rate for biochemical recurrence in patients with negative findings on conventional PSMA PET/CT, achieving a sensitivity of 74.3%. PSA level and PSA doubling time represent predictive biomarkers for lesion detection on [ ⁸⁹ Zr]Zr-PSMA-617 PET/CT. Pending forthcoming prospective studies validating its apparently exceptional clinical potential, [ ⁸⁹ Zr]Zr-PSMA-617 PET/CT may serve as a useful complementary imaging approach, enabling and facilitating individualized and targeted therapeutic approaches including curative salvage treatment in non-advanced prostate cancer disease.

Introduction: To enhance the effectiveness of radioligand therapy (RLT), new prostate-specific membrane antigen (PSMA) targeting radiopharmaceuticals utilizing alternative radionuclides are under active investigation. One promising alternative to the established ¹⁷⁷ Lu is the use of ¹⁶¹ Tb. A key advantage of ¹⁶¹ Tb is its emission of a higher proportion of low-energy conversion and Auger electrons, which may contribute to enhanced therapeutic effectiveness. This study provides a first exploratory evaluation of the efficacy and safety of [ ¹⁶¹ Tb]Tb-PSMA-617 in patients with progression after [ ¹⁷⁷ Lu]Lu-PSMA-617, aiming to generate early clinical insights. Methods: The study included 15 patients with mCRPC, who were enrolled in the “prospective registry to assess outcome and toxicity of targeted radionuclide therapy in patients with mCRPC in clinical routine“ (REALITY Study; NCT04833517). All patients had received conventional PSMA RLT using [ ¹⁷⁷ Lu]Lu-PSMA-617, which resulted in initial biochemical response (PSA decline ≥50%), followed by a biochemical relapse, prompting the re-initiation of PSMA RLT using [ ¹⁶¹ Tb]Tb-PSMA-617. Patients received a median of 3 (range: 2–7) cycles with mean administered activity of 5.4 ± 1.1 GBq and mean cumulative activity of 19.2 ± 6.4 GBq [ ¹⁶¹ Tb]Tb-PSMA-617. Treatment response was assessed both biochemically by serum PSA levels and through molecular imaging by total lesion PSMA (TLP) on [ ⁶⁸ Ga]Ga-PSMA-11 PET/CT scans. Adverse events were assessed at baseline and follow-up using the “Common Terminology Criteria for Adverse Events“ (Version 5.0). Results: [ ¹⁶¹ Tb]Tb-PSMA-617 RLT showed response rates of 66.7% (10/15 patients) based on biochemical assessment and 86.7% (13/15 patients) based on molecular imaging assessment. Beginning with the initiation of [ ¹⁶¹ Tb]Tb-PSMA-617 RLT, the median progression-free survival (PFS) was 6.4 months, and the median overall survival (OS) was 15.5 months. In total, 6 CTCAE grade deteriorations from grade 2 to grade 3 or from grade 3 to grade 4 were observed. No discontinuation of PSMA RLT due to adverse events was reported. Conclusions: [ ¹⁶¹ Tb]Tb-PSMA-617 RLT emerges as a promising treatment option, demonstrating encouraging response rates, preliminary clinical outcomes, and a favorable safety profile as second-line RLT in progressing patients who previously benefited from [ ¹⁷⁷ Lu]Lu-PSMA-617 RLT.

Background: The definite diagnosis of Parkinson’s disease (PD) is usually made by the detection of α-synuclein aggregates in the brain post mortem with the rare exception of some genetic forms. Traces of α-synuclein aggregates in extracerebral tissue biopsies may serve as an appropriate biomarker to confirm a clinical diagnosis in vivo . Objectives: We set out to determine whether the detection of α-synuclein aggregates in submandibular gland biopsies is an effective means for diagnosing PD patients. Methods: We examined submandibular gland biopsies from 25 patients with PD under investigation and 25 age-matched controls to detect α-synuclein aggregates using real-time quaking induced conversion (RT-QuIC) as a seed amplification-assay and immunohistochemical α-synuclein aggregate detection and paraffin-embedded tissue blot (PET-blot) as confirmatory methods. Results: Our RT-QuIC assay detected α-synuclein aggregates in submandibular gland biopsies with a sensitivity of 81,1%, which increased to 90% after a clinical follow-up, and a specificity of 100%. The PET-blot with mAb5C12 confirmed 50% of the RT-QuIC positives and offered a sensitivity of 45,8% (50% after clinical follow-up) and a specificity of 100%. Immunohistochemical detection using the same antibody confirmed 28% of the RT-QuIC positives, but found two of the controls to be positive and therefore provided a sensitivity of 26,1% (28,6% after clinical follow-up) and a specificity of 92%. Conclusions: The RT-QuIC Assay demonstrated comparable sensitivity to the clinical diagnosis (when neuropathologic examination represents the gold standard) and exhibited a similar level of specificity as the PET-blot.

Background: Risk assessment in hyperthyroidism remains challenging. The aim of the present study is to determine the influence of hyperthyroid metabolic status on blood clotting and an increased risk of thrombosis. Methods: This prospective study included 50 patients after radical thyroidectomy and ablative radioiodine therapy because of thyroid carcinoma who were compared with 50 control subjects in a euthyroid metabolic state. Latent hyperthyroid patients with basal thyroid-stimulating hormone (TSH) ≤ 0.15 mU/L on levothyroxine hormone therapy were included. The control group was selected to match the patient group based on age and sex. The evaluation data were collected using laboratory coagulation tests and patient questionnaires. A bleeding and a thrombosis score were determined. Results: The coagulation parameters between the patient and control groups showed statistically significant differences. In particular, the patients’ group showed a significantly shortened activated partial thromboplastin time (aPTT/p = 0.009) and a significantly higher plasminogen activator inhibitor 1 (PAI-1/p < 0.001) compared to the control group. Age, sex, and medication use were not found to influence the patients’ laboratory results. Only body mass index was higher in the patient group than in the control group. Conclusions: Our results support a shift in the coagulation system in latent hyperthyroid metabolism towards increased coagulability and reduced fibrinolysis. A latent hyperthyroid metabolic state appears to be associated with an increased risk of thrombosis. Further prospective cohort studies with large patient populations are needed to verify the association between (latent) hyperthyroidism and thromboembolic events as well as to determine therapeutic anticoagulation or to adjust the indication for exogenous administration of thyroid hormone.