Background: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with ¹⁷⁷Lu-labeled PSMA ligands has achieved remarkable results in advanced disease stages of metastatic castration-resistant prostate cancer (mCRPC). However, not all patients benefit from this therapy. Different treatment responses could be explained by tumor heterogeneity triggered by progression and the number of prior treatments. PSMA-negative lesions can be missed on PSMA ligand PET/CT, which subsequently results in an underestimation of tumor burden. Conversely, high FDG uptake may also be an indicator of tumor aggressiveness and thus a poor prognostic marker for response to RLT and overall survival (OS). The aim of this analysis was to investigate the prognostic value of combined PSMA ligand PET/CT and [¹⁸F]fluorodeoxyglucose (FDG) PET/CT for outcome prediction in patients undergoing RLT. Materials and methods: This bicentric analysis included 54 patients with mCRPC who underwent both FDG and PSMA ligand PET/CT imaging before RLT. In all patients, the pattern of PSMA ligand and FDG uptake was visually assessed. Patients with at least one FDG-positive, but PSMA-negative (FDG+/PSMA−) lesions were compared to patients without any FDG+/PSMA− lesions. A log-rank analysis was used to assess the difference in OS between subgroups. Results: Median OS was 11 ± 1.8 months (95% CI 7.4–14.6). A significantly lower OS (p < 0.001) was found in patients with at least one FDG+/PSMA− lesion at baseline PET/CTs (n = 18) with a median OS of 6.0 ± 0.5 months (95% CI: 5.0–7.0 months). In comparison, patients without any FDG+/PSMA− lesions (n = 36) had a median OS of 16.0 ± 2.5 months (95% CI: 11.2–20.8 months). Conclusion: FDG+/PSMA− lesions are a negative predictor of overall survival in patients with mCRPC undergoing RLT. However, it remains to be determined if patients with FDG+/PSMA− lesions should be excluded from PSMA RLT.

An increasing number of International Medical Graduates (IMG), who are defined to be physicians working in a country other than their country of origin and training, immigrate to Western countries. In order to ensure safe and high-quality patient care, they have to take medical and language tests. This systematic review aims to (1) collect all empiric research on intercultural communication of IMGs in medical settings, (2) identify and categorize all text passages mentioning intercultural issues in the included studies, and (3) describe the most commonly reported intercultural areas of communication of IMGs. This review was based on the PRISMA-Guidelines for systematic reviews. We conducted a broad and systematic electronic literature search for empiric research in the following databases: MEDLINE, BIOSIS Citation Index, BIOSIS Previews, KCI-Korean Journal Database and SciELO Citation Index. The search results were synthesized and analyzed with the aid of coding systems. These coding systems were based on textual analysis and derived from the themes and topics of the results and discussion sections from the included studies. A quality assessment was performed, comparing the studies with their corresponding checklist (COREQ or STROBE). Textual results of the studies were extracted and categorized. Among 10,630 search results, 47 studies were identified for analysis. 31 studies were qualitative, 12 quantitative and 4 studies used mixed methods. The quality assessment revealed a low level of quality of the studies in general. The following intercultural problems were identified: IMGs were not familiar with shared decision-making and lower hierarchies in the health care system in general. They had difficulties with patient-centered care, the subtleties of the foreign language and with the organizational structures of the new health care system. In addition, they described the medical education in their home countries as science-oriented, without focusing on psychosocial aspects. There is a need for a better training of IMGs on culture-related and not culture-related topics in the new workplace country. The topics that emerged in this review constitute a basis for developing these courses. Further empiric research is needed to describe the findings of this review more precisely and should be in accordance with the existing reporting guidelines.

Introduction: Positron emission tomography/computer tomography (PET/CT) targeting the prostate specific membrane antigen (PSMA) plays a key role in staging of patients with prostate cancer (PCa). Moreover, it is not only used for the assessment of adequate PSMA expression of PCa cells before PSMA-targeting radioligand therapy (PSMA RLT) but also for re-staging during the course of therapy to evaluate response to treatment. Whereas no established criteria exist for systematic response evaluation so far, recently proposed PSMA PET Progression (PPP) criteria might fill this gap. The aim of this study was to assess the feasibility of PPP criteria in patients undergoing PSMA RLT and their prognostic implications. Methods: In this retrospective analysis, PSMA PET/CT scans of 46 patients acquired before and after completion of PSMA RLT were analyzed separately by two readers using modified PPP criteria. After interobserver agreement assessment, consensus results (progressive vs. non-progressive disease) were compared in a multivariate cox regression model (endpoint overall survival, OS). Results: Interobserver agreement on modified PPP criteria was substantial (Cohens κ = 0.73) with a concordance in 87% of patients. Median OS of all patients after PSMA RLT (n = 46) was 9.0 [95% confidence interval (CI) 7.8 - 10.2] months. Progression according to modified PPP criteria was found in 32 patients and was a significant (p ≤0.001) prognostic marker for OS with a hazard ratio of 15.5 [95% CI 3.4 - 70.2]. Conclusion: Response assessment in patients undergoing PSMA RLT using modified PPP criteria are reproducible and highly prognostic for OS. Modified PPP criteria should be validated in future prospective trials.

Introduction: Quantitative evaluation of prostate-specific membrane antigen (PSMA)- targeting positron emission tomography/computer tomography (PSMA PET/CT) remains challenging but is urgently needed for the use of standardized PET-based response criteria, such as the PSMA PET/CT consensus statement or RECIP 1.0. A recent study evaluated the prognostic value of whole-body tumor volume using a semiautomatical method relying on a 50% threshold of maximum lesion standardized uptake value (PSMA_TV50). In the present study, we analyzed the suitability of this approach comparing ¹⁸F-PSMA-1007 to ⁶⁸Ga-PSMA-11 PET/CT scans and the potential of PSMA_TV50 for the prediction of overall survival (OS) in patients before ¹⁷⁷Lu-PSMA-radioligand therapy (PSMA RLT). Moreover, PSMA_TV50 was integrated into the PSMA PET/CT consensus statement as well as RECIP 1.0 and the prognostic value of these response classification systems was compared. Methods: This retrospective study included 70 patients with metastatic castration-resistant prostate cancer undergoing PSMA RLT. 33 patients were monitored by ⁶⁸Ga-PSMA-11 PET/CT and 37 patients by ¹⁸F-PSMA-1007 PET/CT. PET/CT scans before (baseline) and at the end of PSMA RLT after 2-4 cycles (follow-up) were separately analyzed by two readers. PSMA_TV50 at baseline and its change to follow-up (ΔPSMA_TV50; expressed as a ratio) were correlated with OS using Cox proportional hazard regression. The results of both subgroups were compared. The integration of ΔPSMA_TV50 in existing response classification systems was evaluated. To assess and compare the discriminatory strength of these classification systems, Gönen & Heller concordance probability estimates (CPE) were calculated. Results: PSMA_TV50-determination was technically feasible in all examinations. A higher PSMA_TV50 at baseline and a higher ΔPSMA_TV50 were strongly associated with a shorter OS for both ⁶⁸Ga-PSMA-11 (PSMA_TV50: HR 1.29 [1.05 – 1.55], p=0.009; ΔPSMA_TV50: HR 1.83 [1.08 – 3.09], p=0.024) and ¹⁸F-PSMA-1007 (PSMA_TV50: HR 1.84 [1.13 – 2.99], p=0.014; ΔPSMA_TV50: HR 1.23 [1.04 – 1.51], p=0.03). Response assessment provided high discriminatory power for OS for the PSMA PET/CT consensus statement (CPE 0.73) as well as RECIP 1.0 (CPE 0.74). Conclusion: PSMA_TV50 and ΔPSMA_TV50 proved to be predictive of OS not only for ⁶⁸Ga-PSMA-11 but also for ¹⁸F-PSMA-1007 PET/CT scans. Subsequent integration of ΔPSMA_TV50 into the PSMA PET/CT consensus statement and RECIP 1.0 provided equally high prognostic value for both classification systems.

Background: Positron emission tomography (PET)/computed tomography (CT) using the gastrin-releasing peptide receptor antagonist [⁶⁸Ga]RM2 has shown to be a promising imaging method for primary breast cancer (BC) with positive estrogen receptor (ER) status. This study assessed tumor visualization by [⁶⁸Ga]RM2 PET/CT in patients with pre-treated ER-positive BC and suspected metastases. Methods: This retrospective pilot study included eight female patients with initial ER-positive, pre-treated BC who underwent [⁶⁸Ga]RM2 PET/CT. Most of these patients (seven out of eight; 88%) were still being treated with or had received endocrine therapy. [⁶⁸Ga]RM2 PET/CTs were visually analyzed by two nuclear medicine specialists in consensus. Tumor manifestations were rated qualitatively (i.e., RM2-positive or RM2-negative) and quantitatively using the maximum standardized uptake value (SUVmax). SUVmax values were compared between the two subgroups (RM2-positive vs. RM2-negative). Results: Strong RM2 binding was found in all metastatic lesions of six patients (75%), whereas tracer uptake in all metastases of two patients (25%) was rated negative. Mean SUVmax of RM2-positive metastases with the highest SUVmax per patient (in lymph node and bone metastases; 15.8 ± 15.1 range: 3.7–47.8) was higher than mean SUVmax of the RM2-negative metastases with the highest SUVmax per patient (in bone metastases; 1.6 ± 0.1, range 1.5–1.7). Conclusions: Our data suggest that RM2 binding is maintained in the majority of patients with advanced disease stage of pre-treated ER-positive BC. Thus, [⁶⁸Ga]RM2 PET/CT could support treatment decision in these patients, radiotherapy planning in oligometastatic patients or selection of patients for RM2 radioligand therapy. Further studies with larger patient cohorts are warranted to confirm these findings.

Aim In patients with metastasized castration-resistant prostate cancer a reliable imaging-based therapy response assessment in addition to PSA kinetics is desirable. Recently, measurements of whole-body tumour burden by [⁶⁸Ga]PSMA-11 PET/CT have been reported for response assessment in oligometastasic patients. The present study investigated the association of PSMA PET derived parameters and serum PSA level before and after [¹⁷⁷Lu]PSMA-617 radioligand therapy (RLT). Methods This retrospective study assessed whole-body PSMA tumour volume (PSMA-TV) in 10 patients with multifocal to diffuse metastases before and after 2 cycles of RLT using volume of interest (VOI) analysis. A standardized uptake value (SUV) threshold-based approach was used to semi-automatically delineate all voxels with a SUV ≥ 2.0 g/ml using the software ROVER^® (ABX Radeberg, Germany). Voxels with physiological tracer uptake (e. g. kidneys) were excluded manually. Correlations between PSMA-TV and serum PSA level before and after two cycles of RLT as well as changes thereof (ΔPSMA-TV and ΔPSA, respectively) were calculated. Results Changes of ΔPSMA-TV and ΔPSA were concordant in 7 of 10 patients. Whereas a good correlation was found between PSMA-TV and PSA before RLT (ρ = 0.81, p = 0.0049), this correlation was attenuated after RLT (ρ = 0.64, p = 0.0479). Consequently, no association was found between ΔPSMA-TV and ΔPSA (ρ = 0.39, p = 0.26). Conclusion The attenuation of the correlation of PSA and PSMA-TV after RLT suggests that in patients with advanced disease the comparison of imaging based parameters such as PSMA-TV and PSA level might be useful for an adequate monitoring of treatment response. Ziel Bei Patienten mit fortgeschrittenem metastasiertem Prostatakarzinom stehen neben dem PSA-Verlauf nur eingeschränkt Bildgebungsresponsekriterien zur Verfügung. Studien legen jedoch bei oligometastasierten Patienten nach Chemotherapie oder antihormoneller Therapie eine bildgebende Responseabschätzung anhand PET-basierter Ganzkörper-PSMA-Tumorlast nahe. Ziel dieser Studie war es, den Zusammenhang zwischen PSMA-PET-basierten Parametern und dem PSA-Wert bei Patienten vor und nach [¹⁷⁷Lu]PSMA-617-Radioligandentherapie (RLT) zu untersuchen. Methodik Das Ganzkörper-PSMA-Tumorvolumen (PSMA-TV) und der PSA-Wert wurden bei 10 Patienten mit ausgeprägter, teils disseminierter Knochenmetastasierung vor und nach 2 Zyklen RLT retrospektiv bestimmt. Unter Verwendung eines absoluten Schwellwertes von SUV > 2,0 g/ml wurden alle Tumorareale semiautomatisch mittels der Software ROVER^® (ABX Radeberg, Germany) konturiert. Nach der Entfernung von Voxeln mit physiologischer Tracerbelegung (z. B. Nieren) wurde das PSMA-TV bestimmt. Die Korrelation zwischen PSMA-TV und PSA-Wert vor bzw. nach 2 Zyklen RLT sowie die der jeweiligen prozentualen Änderung (ΔPSMA-TV und ΔPSA) wurden bestimmt. Ergebnisse Es fand sich eine Übereinstimmung der prozentualen Änderung von ΔPSMA-TV und ΔPSA bei 7 von 10 Patienten. Während sich vor RLT eine gute Korrelation zwischen den PSA- und PSMA-TV-Werten (ρ = 0,81; p = 0,0049) zeigte, nahm diese nach 2 Zyklen ab (ρ = 0,64; p = 0,0479). Entsprechend zeigte sich keine Korrelation zwischen ΔPSMA-TV und ΔPSA (ρ = 0,39; p = 0,26). Schlussfolgerungen Die Abnahme der Korrelation von PSMA-TV und PSA nach RLT suggeriert, dass bei Patienten mit fortgeschrittener Erkrankung die Bestimmung bildgebender Parameter, wie z. B. PSMA-TV, zusätzlich zur PSA-Messung sinnvoll sein könnte, um das Therapieansprechen besser abschätzen zu können.