We aimed to evaluate the predictive and prognostic value of baseline ¹⁸F-FDG-PET-CT (PET-CT) radiomic features (RFs) for immune checkpoint-inhibitor (CKI)-based first-line therapy in advanced non-small-cell lung cancer (NSCLC) patients. In this retrospective study 44 patients were included. Patients were treated with either CKI-monotherapy or combined CKI-based immunotherapy–chemotherapy as first-line treatment. Treatment response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). After a median follow-up of 6.4 months patients were stratified into “responder” (n = 33) and “non-responder” (n = 11). RFs were extracted from baseline PET and CT data after segmenting PET-positive tumor volume of all lesions. A Radiomics-based model was developed based on a Radiomics signature consisting of reliable RFs that allow classification of response and overall progression using multivariate logistic regression. These RF were additionally tested for their prognostic value in all patients by applying a model-derived threshold. Two independent PET-based RFs differentiated well between responders and non-responders. For predicting response, the area under the curve (AUC) was 0.69 for “PET-Skewness” and 0.75 predicting overall progression for “PET-Median”. In terms of progression-free survival analysis, patients with a lower value of PET-Skewness (threshold < 0.2014; hazard ratio (HR) 0.17, 95% CI 0.06–0.46; p < 0.001) and higher value of PET-Median (threshold > 0.5233; HR 0.23, 95% CI 0.11–0.49; p < 0.001) had a significantly lower probability of disease progression or death. Our Radiomics-based model might be able to predict response in advanced NSCLC patients treated with CKI-based first-line therapy.

Sarcoidosis is a multisystem disorder of unknown etiology. The leading hypothesis involves an antigen-triggered dysregulated T-cell-driven immunologic response leading to non-necrotic granulomas. In cardiac sarcoidosis (CS), the inflammatory response can lead to fibrosis, culminating in clinical manifestations such as atrioventricular block and ventricular arrhythmias. Cardiac manifestations frequently present as first and isolated signs or may appear in conjunction with extracardiac manifestations. The incidence of sudden cardiac death (SCD) is high. Diagnosis remains a challenge. For a definite diagnosis, endomyocardial biopsy (EMB) is suggested. In clinical practice, compatible findings in advanced imaging using cardiovascular magnetic resonance (CMR) and/or positron emission tomography (PET) in combination with extracardiac histological proof is considered sufficient. Management revolves around the control of myocardial inflammation by employing immunosuppression. However, data regarding efficacy are merely based on observational evidence. Prevention of SCD is of particular importance and several guidelines provide recommendations regarding device therapy. In patients with manifest CS, outcome data indicate a 5-year survival of around 90% and a 10-year survival in the range of 80%. Data for patients with silent CS are conflicting; some studies suggest an overall benign course of disease while others reported contrasting observations. Future research challenges involve better understanding of the immunologic pathogenesis of the disease for a targeted therapy, improving imaging to aid early diagnosis, assessing the need for screening of asymptomatic patients and randomized trials.

[¹⁸F]tetrafluoroborate ([¹⁸F]TFB) is an emerging PET tracer with excellent properties for human sodium iodide symporter (NIS)–based imaging in patients with differentiated thyroid cancer (DTC). The aim of this study was to compare [¹⁸F]TFB PET with high-activity posttherapeutic [¹³¹I]iodine whole-body scintigraphy and SPECT/CT in recurrent DTC and with [¹⁸F]FDG PET/CT in suspected dedifferentiation. Methods: Twenty-six patients treated with high-activity radioactive [¹³¹I]iodine therapy (range, 5.00–10.23 GBq) between May 2020 and November 2022 were retrospectively included. Thyroid-stimulating hormone was stimulated by 2 injections of recombinant thyroid-stimulating hormone (0.9 mg) 48 and 24 h before therapy. Before treatment, all patients underwent [¹⁸F]TFB PET/CT 40 min after injection of a median of 321 MBq of [¹⁸F]TFB. To study tracer kinetics in DTC lesions, 23 patients received an additional scan at 90 min. [¹³¹I]iodine therapeutic whole-body scintigraphy and SPECT/CT were performed at a median of 3.8 d after treatment. Twenty-five patients underwent additional [¹⁸F]FDG PET. Two experienced nuclear medicine physicians evaluated all imaging modalities in consensus. Results: A total of 62 suspected lesions were identified; of these, 30 lesions were [¹³¹I]iodine positive, 32 lesions were [¹⁸F]TFB positive, and 52 were [¹⁸F]FDG positive. Three of the 30 [¹³¹I]iodine-positive lesions were retrospectively rated as false-positive iodide uptake. Tumor-to-background ratio measurements at the 40- and 90-min time points were closely correlated (e.g., for the tumor-to-background ratio for muscle, the Pearson correlation coefficient was 0.91; P < 0.001; n = 49). We found a significant negative correlation between [¹⁸F]TFB uptake and [¹⁸F]FDG uptake as a potential marker for dedifferentiation (Pearson correlation coefficient, −0.26; P = 0.041; n = 62). Conclusion: Pretherapeutic [¹⁸F]TFB PET/CT may help to predict the positivity of recurrent DTC lesions on [¹³¹I]iodine scans. Therefore, it may help in the selection of patients for [¹³¹I]iodine therapy. Future prospective trials for iodine therapy guidance are warranted. Lesion [¹⁸F]TFB uptake seems to be inversely correlated with [¹⁸F]FDG uptake and therefore might serve as a dedifferentiation marker in DTC. Visual Abstract

A 72-year-old man revealed typical findings of cardiac sarcoidosis on cardiovascular MRI. However, ¹⁸F-FDG PET showed no hypermetabolism. Therefore, immunosuppression was not initiated. After 2 years, ventricular arrhythmias and heart failure worsened. ⁶⁸Ga–fibroblast activation protein inhibitor PET was initiated to evaluate potential adverse remodeling due to progressive myocardial fibrosis. A second ¹⁸F-FDG PET still revealed no hypermetabolism, and the patient received an implanted cardioverter defibrillator after electrophysiological risk stratification. We present a case of intense fibroblast activation despite a missing ¹⁸F-FDG uptake (mismatch).

Background: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) is an essential tool for patient selection before radioligand therapy (RLT). Interim-staging with PSMA-PET during RLT allows for therapy monitoring. However, its added value over post-treatment imaging is poorly elucidated. The aim of this study was to compare early treatment response assessed by post-therapeutic whole-body scans (WBS) with interim-staging by PSMA-PET after 2 cycles in order to prognosticate OS. Methods: Men with metastasized castration-resistant PC (mCRPC) who had received at least two cycles of RLT, and interim PSMA-PET were evaluated retrospectively. PROMISE V2 framework was used to categorize PSMA expression and assess response to treatment. Response was defined as either disease control rate (DCR) for responders or progression for non-responders. Results: A total of 188 men with mCRPC who underwent RLT between February 2015 and December 2021 were included. The comparison of different imaging modalities revealed a strong and significant correlation with Cramer V test: e.g. response on WBS during second cycle compared to interim PET after two cycles of RLT (c_φ = 0.888, P < 0.001, n = 188). The median follow-up time was 14.7 months (range: 3–63 months; 125 deaths occurred). Median overall survival (OS) time was 14.5 months (95% CI: 11.9–15.9). In terms of OS analysis, early progression during therapy revealed a significantly higher likelihood of death: e.g. second cycle WBS (15 vs. 25 months, P < 0.001) with a HR of 2.81 (P < 0.001) or at PET timepoint after 2 cycles of RLT (11 vs. 24 months, P < 0.001) with a HR of 3.5 (P < 0.001). For early biochemical response, a PSA decline of at least 50% after two cycles of RLT indicates a significantly lower likelihood of death (26 vs. 17 months, P < 0.001) with a HR of 0.5 (P < 0.001). Conclusion: Response assessment of RLT by WBS and interim PET after two cycles of RLT have high congruence and can identify patients at risk of poor outcome. This indicates that interim PET might be omitted for response assessment, but future trials corroborating these findings are warranted.

Background: Small-cell lung cancer (SCLC) is a highly malignant disease with a propensity for early progression and high mortality. The prognostic value of treatment response and survival has been verified for solely established imaging, clinical, and biochemical markers. There is a lack of evidence for the combination of those parameters with machine learning and integrated models, particularly in the context of molecular imaging. Objectives: The aim of this study was to predict early disease progression and survival using CT-based radiomic features (RF), integrating [ ¹⁸ F]FDG-PET-CT and clinical parameters. Design: This retrospective pilot study included 62 patients with non-metastatic and metastatic SCLC who underwent stage-based primary treatment following baseline [ ¹⁸ F]FDG-PET-CT. The development of a machine learning approach, incorporating clinical and molecular imaging parameters, enables the creation of a model capable of predicting treatment response and survival. Methods: A radiomics signature was generated based on the first-line treatment response by RECIST 1.1 criteria. The RF was integrated using binary logistic regression analysis with the PET parameter metabolic tumor volume (MTV) of the primary tumor and initial disease stage. The integrated model with the highest AUC for predicting early disease progression was evaluated for predicting progression-free survival (PFS) and overall survival (OS) in both non-metastatic and metastatic patients. Results: A single CT-based RF demonstrated predictive capacity (AUC = 0.81). Integration of the MTV and disease stage enhanced the predictive capacity (AUC = 0.9). A Youden index-based threshold of <0.62 was identified as a significant predictor of prolonged PFS: non-metastatic disease with a median PFS of 25 versus 4 months (HR = 0.072; p = 0.002); metastatic disease with a median PFS of 9 versus 5 months (HR 0.219; p = 0.004). The integrated model also predicted OS in metastatic disease with a median OS of 15 versus 8 months (HR 0.381; p = 0.013). Conclusion: A multiparametric approach based on a Radiomics model may potentially be capable of identifying patients at risk for early disease progression, PFS, and OS in non-metastatic and metastatic SCLC.