Ethische Herausforderungen bei der sozialwissenschaftlichen Analyse von Social-Media-Inhalten

"Social-Media-Analyse (SMA)-Techniken ermöglichen es zehn Jahre nach der Einführung von Facebook, das Web-2.0-Publikationsverhalten von BürgerInnen auch in gesellschaftlich relevanten Politikfeldern wie der Integration von MigrantInnen für wissenschaftliche Institutionen und öffentliche Verwaltungen zu erforschen. Am Fallbeispiel des von der EU-Kommission geförderten Forschungs- und Entwicklungsprojekts 'UniteEurope' untersucht der vorliegende Artikel die ethischen Bedingungen, unter denen solche Analysen stattfinden können. Dabei stehen zwei Aspekte im Vordergrund: Zum einen geht es um den Schutz der Privatsphäre von AutorInnen der erforschten Inhalte. Zum anderen beleuchtet der Artikel Möglichkeiten von Social-Media-Analyse-Technologien, die fehlende gesellschaftliche Repräsentativität im Internet zu berücksichtigen, ohne die Ergebnisse quantitativ zu gewichten." (Autorenreferat)"Ten years after the launch of Facebook, social-media-analysis (SMA) technologies make it possible for scientific institutions as well as public authorities to investigate Web 2.0 postings of citizens in socially relevant policy fields such as migrant integration. Using the case of the European Commission's funded research and development project 'UniteEurope', this article examines the ethical conditions that are necessary for such analysis. Thereby, two aspects appear to be crucial: On the one hand, this article raises questions of privacy of the original authors who posted the researched content. On the other hand, the article also explores possible measures that social-media-analysis technologies can employ in order to consider the missing representativeness of the Internet, without introducing a quantitative weighting of results." (author's abstract

Staging performance and clinical impact of 68Ga-PSMA 11 ligand PET imaging in patients with primary prostate cancer and in patients with biochemical recurrence after radical prostatectomy

Hintergrund und Ziele: Das Staging beim Prostatakarzinom (PC) verlässt sich auf bildgebende Techniken, die in allen Stadien der Erkrankung erhebliche Schwächen aufweisen. Das Ziel dieser Arbeit war es, die diagnostische Leistung und den klinischen Nutzen der [68Ga]Ga-prostate specific membrane antigen-11 (PSMA)- positron emission tomography (PET) bei Patienten mit einem neu diagnostizierten PC und bei Patienten mit einem biochemischen Rezidiv (BCR) nach radikaler Prostatektomie (RP) zu untersuchen. Um diese Ziele zu erreichen führten wir zwei verschiedene Studien durch. Material und Methoden: Studie eins war eine retrospektive Untersuchung von 117 hormon-naiven BCR-Patienten nach RP, die mittels PSMA-PET/CT (n=46) oder PSMA-PET/MRT (n=71) gestaged wurden. BCR wurde als ein PSA-Anstieg >0.2 ng/ml definiert. Alle Patientenfälle wurden in einem retrospektiven Tumorboard besprochen, um den klinischen Nutzen der PSMA-PET hinsichtlich der Änderungen im Therapiemanagement zu ermitteln. Studie zwei war eine prospektive diagnostische Studie bei Patienten mit einem bioptisch verifizierten PC, die zur RP an unser Zentrum überwiesen wurden. Es konnten 122 Patienten eingeschlossen werden, die vor der geplanten Therapie eine PSMA-PET/MRT hatten. Die Ergebnisse des Stagings wurden mittels Histologie nach RP bestätigt. Nach dem PSMA-PET/MRT überdachte ein interdisziplinäres Tumorboard den initialen therapeutischen Plan. Ergebnisse: Studie eins: Bei einem medianen PSA-Wert von 1.04 ng/ml (IQR 58-187) konnten wir PSMA-positive Läsionen in 85.5% der Patienten detektieren (100/117). Eine Korrelierung mit den PSA-Werten zeigte Detektionsraten von 65% für einen PSA-Wert von 0.2 bis <0.5 ng/ml mit Steigerung auf 100% bei PSA-Werten 2 ng/ml. Die Verifizierung der Läsionen gelang in 79% der Fälle. Die PSMA-PET änderte das therapeutische Vorgehen in nahezu 75% der Patienten. Studie zwei: Die PSMA-PET/MRT identifizierte den Tumor in der Prostata in 97.5% der Patienten und sie änderte das therapeutische Management in 28.7% aller Patientenfälle. 81 Patienten unterzogen sich nach der Bildgebung nach wie vor einer RP. Eine Patienten-basierte Untersuchung zeigte eine Vorhersagewahrscheinlichkeit für den Lymphknotenstatus von 93% (Sensitivität 68-8%, Spezifität 100%). Die Vorhersagewahrscheinlichkeit für den T-Status war 82.5% (95%CI 72-90, p<0.001). Schlussfolgerungen: Die PSMA-PET zeigte eine exzellente diagnostische Leistung in beiden Stadien der Erkrankung und änderte den Therapieplan in einer großen Zahl der Patienten.Background and objective: Staging of prostate cancer (PC) counts on imaging techniques, which are limited in any state of the disease. The aim of this thesis was to evaluate the diagnostic efficacy and clinical benefit of [68Ga]Ga-prostate specific membrane antigen-11 (PSMA)- positron emission tomography (PET) in patients with primary diagnosed PC and in patients with recurrent PC (BCR) after definitive local treatment for localized PC. To address these aims we conducted two different studies. Material and methods: Study one was a retrospective assessment of 117 BCR patients after radical prostatectomy (RP) (hormone-naïve) undergoing PSMA-PET/CT (n=46) or PSMA-PET/MRI (n=71). BCR was considered as a PSA rise of >0.2 ng/ml. All patient cases were discussed in a retrospective tumorboard to evaluate the impact of PSMA-PET on the clinical decision-making process. Study two was a prospective diagnostic study in patients with biopsy proven PC referred to our center for RP. 122 patients could be included and PSMA-PET/MRI was performed prior to the planned therapy. The staging results were confirmed using whole-mount histopathology of RP specimen. After PSMA-PET/MRI a interdisciplinary tumorboard reassessed the initial planned therapy approach to evaluate the clinical impact also here. Results: Study one: At a median PSA of 1.04 ng/ml (IQR 58-187) we could identify PSMA-positive lesions in 85.5% of the patients (100/117). A correlation to the PSA levels showed a detection efficacy of 65% for a PSA level of 0.2 to <0.5 ng/ml, increasing to 100% if the PSA was higher than 2 ng/ml. Lesion verification was achieved in 79% of all patients. PSMA-PET changed the therapeutic strategy in almost 75% of the patients significantly, with almost 90% of them being referred to metastases-directed salvage therapies. Study two: PSMA-PET/MRI identified PC in 97.5% of the patients and changed the therapeutic strategy in 28.7% of all patient cases (either onset of systemic therapy/radiotherapy or active surveillance). 81 patients still underwent RP after imaging. A patient based analysis for prediction of the lymph node status assessed an accuracy of 93% (sensitivity 68.8%, specificity 100%). The overall accuracy for T-staging was 82.5% (95%CI 72-90; p<0.001). PSMA-PET/MRI correctly detected organ confined disease with 85% accuracy, extraprostatic tumor growth with 79.1% accuracy and invasion of seminal vesicles with 94.7% accuracy. Conclusions: PSMA-PET showed an excellent diagnostic efficacy in both disease states and changed the treatment strategy in a high number of patients.submitted by Bernhard GrubmüllerAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersMedizinische Universität Wien, Diss., 2018(VLID)280866

Dual-Tracer PET-MRI-Derived Imaging Biomarkers for Prediction of Clinically Significant Prostate Cancer

Purpose: To investigate if imaging biomarkers derived from 3-Tesla dual-tracer [(18)F]fluoromethylcholine (FMC) and [68Ga]Ga-PSMAHBED-CC conjugate 11 (PSMA)-positron emission tomography can adequately predict clinically significant prostate cancer (csPC). Methods: We assessed 77 biopsy-proven PC patients who underwent 3T dual-tracer PET/mpMRI followed by radical prostatectomy (RP) between 2014 and 2017. We performed a retrospective lesion-based analysis of all cancer foci and compared it to whole-mount histopathology of the RP specimen. The primary aim was to investigate the pretherapeutic role of the imaging biomarkers FMC- and PSMA-maximum standardized uptake values (SUVmax) for the prediction of csPC and to compare it to the mpMRI-methods and PI-RADS score. Results: Overall, we identified 104 cancer foci, 69 were clinically significant (66.3%) and 35 were clinically insignificant (33.7%). We found that the combined FMC+PSMA SUVmax were the only significant parameters (p p = 0.049) for the prediction of csPC. ROC analysis showed an AUC for the prediction of csPC of 0.695 for PI-RADS scoring (95% CI 0.591 to 0.786), 0.792 for FMC SUVmax (95% CI 0.696 to 0.869), 0.852 for FMC+PSMA SUVmax (95% CI 0.764 to 0.917), and 0.852 for the multivariable CHAID model (95% CI 0.763 to 0.916). Comparing the AUCs, we found that FMC+PSMA SUVmax and the multivariable model were significantly more accurate for the prediction of csPC compared to PI-RADS scoring (p = 0.0123, p = 0.0253, respectively). Conclusions: Combined FMC+PSMA SUVmax seems to be a reliable parameter for the prediction of csPC and might overcome the limitations of PI-RADS scoring. Further prospective studies are necessary to confirm these promising preliminary results

Response assessment using 68Ga-PSMA ligand PET in patients undergoing 177Lu-PSMA radioligand therapy for metastatic castration-resistant prostate cancer

Purpose The first aim of this study was to evaluate 68Ga-PSMAHBED-CC conjugate 11 positron emission tomography (PSMA PET) parameters for assessment of response to 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC). The second aim was to investigate factors associated with overall survival (OS). Methods We retrospectively assessed mean standardized uptake values (SUVmean) and total tumor volumes (TTV) on PSMA PET in 38 of 55 mCRPC patients before and after RLT. PSA testing and PSMA PET/CT(MRI) imaging were performed during the 8 weeks before and the 6 weeks after RLT. PSMA PET and CT(MRI) images were reviewed separately according to the modified PET Response Criteria in Solid Tumors (mPERCIST) and RECIST1.1. The results were compared with PSA responses. Associations between OS and the RECIST evaluation and changes in SUVmean, TTV, and PSA, CRP, LDH, hemoglobin and ALP levels were determined in a univariable survival analysis. Results The median PSA level at the time of pretherapy PSMA PET/CT(MRI) was 60.8 ng/ml (IQR 15.4, 264.2 ng/ml). After RLT the median PSA level decreased by 44%, TTV by 45.1%, SUVmean by 25.8% and RECIST by 11.3%. A PSA response was seen in 18 patients (47.4%), stable disease in 12 (31.6%) and progressive disease in 8 (21.1%). Contrary to the changes in SUVmean and the RECIST evaluation, the change in TTV was significantly associated with PSA response (p = 0.15, p = 0.58, and p < 0.001, respectively). After a median follow-up of 17 months (IQR 8.0, 24.2 months), 11 patients (28.9%) had died of their prostate cancer. The changes in both TTV and PSA levels were associated with OS (HR 1.001, 95% CI 11.003, p = 0.04, and HR 1.004, 95% CI 1.0011.008, p = 0.01, respectively), while the changes in SUVmean and the RECIST evaluation were not. The pre-therapy CRP level was also associated with OS (HR 1.07, 95% CI 1.0091.14, p = 0.02). Conclusion TTV on PSMA PET seems to be a reliable parameter for response assessment in mCRPC patients undergoing RLT and might overcome the limitations of RECIST in prostate cancer. Furthermore, the change in TTV was significantly associated with OS in our cohort.(VLID)365981

Renal and Salivary Gland Functions after Three Cycles of PSMA-617 Therapy Every Four Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Background: [177Lu]Lu-PSMA-617 radioligand therapy (PSMA-RLT) could affect kidney and salivary gland functions in metastatic castration-resistant prostate cancer (mCRPC) patients. Methods: We retrospectively analyzed clinical, renal, and salivary scintigraphy data and salivary [68Ga]Ga-PSMA-11 ligand PET scan measures such as metabolic volume and SUVmax values of 27 mCRPC men (mean age 71 ± 7 years) before and 4 weeks after receiving three cycles of PSMA-RLT every 4 weeks. Twenty-two patients additionally obtained renal and salivary scintigraphy prior to each cycle. A one-way ANOVA, post-hoc Scheffé test and Cochran’s Q test were applied to assess organ toxicity. Results: In total, 54 PSMA PET scans, 98 kidney, and 98 salivary scintigraphy results were evaluated. There were no significant differences for the ejection fraction, peak time, and residual activity after 5 min for both parotid and submandibular glands prior to each cycle and 4 weeks after the last cycle. Similarly, no significant differences in serum creatinine and renal scintigraphy parameters were observed prior to each cycle and 4 weeks after the last treatment. Despite there being no changes in the metabolic volume of both submandibular glands, SUVmax values dropped significantly (p &lt; 0.05). Conclusion: Results evidenced no alterations in renal function and only minimal impairment of salivary function of mCRPC patients who acquired an intense PSMA-RLT regimen every 4 weeks

Combining PSA and PET features to select candidates for salvage lymph node dissection in recurrent prostate cancer

Objective: To evaluate the relationship between pre-operative PSA value, 68Ga-prostate-specific-membrane-antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). Patients and methods: The study included 164 patients diagnosed with ≤2 pelvic lymph-node recurrence(s) of PCa documented on 68Ga-PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high-volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (1.5 ng/ml). Clinical recurrence (CR)-free survival after sLND was calculated using multivariable analyses and plotted over pre-operative PSA value. Results: Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre-operative PSA value, with highest rates for patients with pre-operative PSA > 1.5 ng/ml (pelvic-only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre-operative PSA was associated with PSA response (p < 0.0001). There were 51 CRs after sLND. After adjusting for confounders, we found a significant, non-linear relationship between PSA level at sLND and the 12-month CR-free survival (p < 0.0001), with the highest probability of freedom from CR for patients who received sLND at PSA level ≥1 ng/ml. Conclusions: In case of PET-detected nodal recurrences amenable to sLND, salvage surgery was associated with the highest short-term oncologic outcomes when performed in men with PSA ≥ 1 ng/ml. Awaiting confirmatory data from prospective trials, these findings may help physicians to optimize the timing for 68Ga-PSMA PET in biochemical recurrent PCa