[PSMA radioligand therapy in patients with advanced prostate cancer]. / Radionuklidtherapie mit PSMA-Liganden bei fortgeschrittenem Prostatakarzinom.

BACKGROUND: Based on significant progress in recent years, metastatic castration-resistant prostate cancer (mCRPC) patients can be treated better and better. The medications include androgen signaling inhibitors, chemotherapy, 223Ra, and sipuleucel-T. Most patients treated with these agents will still develop primary or secondary resistance against any given drug. The 177Lutetium-PSMA radioligand therapy (177Lu-PSMA-RLT) represents a good reserve option and can be used within compassionate use provisions demonstrating promising efficacy in the majority of patients in Germany. OBJECTIVES: Establishment of status quo of 177Lu-PSMA-RLT in mCRPC in 2020. MATERIALS AND METHODS: Presentation of the therapy landscape in mCRPC and the current evidence on 177Lu-PSMA-RLT after PubMed based literature search. RESULTS: Several larger retrospective studies and the first prospective trials on 177Lu-PSMA-RLT show premature but encouraging evidence on 177Lu-PSMA-RLT to be a promising new option in mCRPC patients. The toxicity profile seems to be favorable. The phase III trial VISION aims to provide evidence for the approval of 177Lu-PSMA-RLT in combination with abiraterone or enzalutamide in patients having been pretreated with enzalutamide or abiraterone and docetaxel. CONCLUSIONS: Despite the promising preliminary results of 177Lu-PSMA-RLT, the efficacy results of VISION need to be awaited prior to using the therapy outside of compassionate use provisions.

[Lutetium-177-PSMA radioligand therapy : Consensus within the framework of GKV-funded care between the university hospitals in Aachen, Bonn, Düsseldorf, Essen, and Cologne and the MDK Nordrhein]. / Lutetium-177-PSMA-Radioligandentherapie : Konsensus im Rahmen der GKV-finanzierten Versorgung zwischen den Hochschulkliniken in Aachen, Bonn, Düsseldorf, Essen und Köln und dem MDK Nordrhein.

In the last 3 years, Lutetium-177 prostate-specific membrane antigen radioligand therapy (Lu-177-PSMA-RLT) has received increasing attention in nuclear medicine as a new form of treatment for castration-resistant metastatic prostate cancer. This therapy combines the radionuclide Lutetium-177, which has been therapeutically used in nuclear medicine for many years, with a molecular target of the transmembrane prostate-specific membrane antigen expressed by prostate cancer cells. Since there are no prospective randomized studies on Lu-177-PSMA-RLT and the question of reimbursement has repeatedly been the subject of review by the MDK Nordrhein (Medischenische Dienst der Krankenversicherung), there was a desire because of the increasing number of patients being treated to clarify under which circumstances Lu-177-PSMA-RLT can be reimbursed by German statutory health insurance. The goals of this article are to help treating physicians understand how this new therapy option works, to integrate it in the overall therapy concept for castration-resistant metastatic prostate cancer, and, above all, to use Lu-177-PSMA-RLT-based on the current data-at the right place in the therapy sequence of castration-resistant metastatic prostate cancer.

External radiation exposure, excretion, and effective half-life in 177Lu-PSMA-targeted therapies.

BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted therapy with 177Lu-PSMA-617 is a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC). To optimize the therapy procedure, it is necessary to determine relevant parameters to define radiation protection and safety necessities. Therefore, this study aimed at estimating the ambient radiation exposure received by the patient. Moreover, the excreted activity was quantified. RESULTS: In total, 50 patients with mCRPC and treated with 177Lu-PSMA-617 (mean administered activity 6.3 ± 0.5 GBq) were retrospectively included in a bi-centric study. Whole-body dose rates were measured at a distance of 2 m at various time points after application of 177Lu-PSMA-617, and effective half-lives for different time points were calculated and compared. Radiation exposure to the public was approximated using the dose integral. For the estimation of the excreted activity, whole body measurements of 25 patients were performed at 7 time points. Unbound 177Lu-PSMA-617 was rapidly cleared from the body. After 4 h, approximately 50% and, after 12 h, approximately 70% of the administered activity were excreted, primarily via urine. The mean dose rates were the following: 3.6 ± 0.7 µSv/h at 2 h p. i., 1.6 ± 0.6 µSv/h at 24 h, 1.1 ± 0.5 µSv/h at 48 h, and 0.7 ± 0.4 µSv/h at 72 h. The mean effective half-life of the cohort was 40.5 ± 9.6 h (min 21.7 h; max 85.7 h). The maximum dose to individual members of the public per treatment cycle was ~ 250 ± 55 µSv when the patient was discharged from the clinic after 48 h and ~ 190 ± 36 µSv when the patient was discharged after 72 h. CONCLUSIONS: In terms of the radiation exposure to the public, 177Lu-PSMA is a safe option of radionuclide therapy. As usually four (sometimes more) cycles of the therapy are performed, it must be conducted in a way that ensures that applicable legal requirements can be followed. In other words, the radiation exposure to the public and the concentration of activity in wastewater must be sub-marginal. Therefore, in certain countries, hospitalization of these patients is mandatory.

PSMA targeted radioligandtherapy in metastatic castration resistant prostate cancer after chemotherapy, abiraterone and/or enzalutamide. A retrospective analysis of overall survival.

AIM: Our aim was to evaluate overall survival and parameters prognosticating longer survival in a large and homogeneous group of patients treated with 177Lu-PSMA-617 radioligand therapy with heavily pretreated advanced metastatic castration resistant prostate cancer. METHODS: A total of 104 patients were treated with 351 cycles of 177Lu-PSMA-617. Prostate specific antigen (PSA) changes after the first cycle of therapy were documented prior to a second cycle. Patients were followed-up for overall survival (OS). Any PSA decline, PSA decline ≥50%, initial PSA, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), visceral metastases and cumulative injected activity were analyzed and evaluated according to OS. Multivariable analysis with parameters with a p-value ≤0.05 in univariate analysis was performed, additionally adjusting for age and presence of visceral metastases. RESULTS: A total of 51 patients (49%) died during the observation period. The majority of patients (97%) presented with bone metastases, 77% with lymph node metastases and 32% with visceral metastases. All patients were treated with at least one line of chemotherapy. Either abiraterone or enzalutamide had been given in 100% of the patients. Any PSA decline occurred in 70 (67%) and a PSA decline ≥50% in 34 (33%) of patients after the first cycle. The median OS was 56.0 weeks (95%CI: 50.5-61.5). Initial PSA decline ≥50%, initial LDH, visceral metastases, second line chemotherapy or prior radium-223 did not have an effect on survival, whereas any initial PSA decline, initial ALP <220 U/L and cumulative injected activity ≥18.8 GBq were associated with a longer survival. A step-by-step analysis revealed a PSA decline ≥20.87% as the most noticeable cut-off prognosticating longer survival, which remained an independent prognosticator of improved OS in the multivariate analysis. CONCLUSION: 177Lu-PSMA-617 RLT is a new effective therapeutic and seems to prolong survival in patients with advanced mCRPC pretreated with chemotherapy, abiraterone and/or enzalutamide.

[177Lu-PSMA therapy : Current evidence for use in the treatment of patients with metastatic prostate cancer]. / 177Lu-PSMA-Therapie : Aktuelle Evidenzlage beim Einsatz in der Behandlung von Patienten mit metastasiertem Prostatakarzinom.

BACKGROUND: Despite significant progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years (including agents targeting androgen receptor signaling, chemotherapy, and 223Ra), most of these patients still succumb to prostate cancer. Recently, 177lutetium prostate-specific membrane antigen radioligand therapy (177Lu-PSMA-RLT) has been increasingly used within compassionate use provisions in these patients in Germany and showed promising efficacy. OBJECTIVES: Establishment of the current position of 177Lu-PSMA-RLT in mCRPC in 2017. MATERIALS AND METHODS: Presentation of the therapy landscape in mCRPC and the current challenges within treatment and survey of the available data on 177Lu-PSMA-RLT after PubMed-based research. RESULTS: In several larger retrospective studies, 177Lu-PSMA-RLT seems to be an encouraging new option with the potential to extend overall survival while displaying a favorable toxicity profile. CONCLUSIONS: Prospective trials are urgently needed to confirm these encouraging results found in retrospective analyses with 177Lu-PSMA-RLT in the treatment of mCRPC.

Evaluation of association between intima-media thickness of the carotid artery and risk factors for cardiovascular disease in patients on maintenance hemodialysis.

Cardiovascular disease is the most common cause of mortality and morbidity in patients with end-stage renal disease (ESRD). Atherosclerosis is a systemic disease, and carotid and coronary vessels are at comparable risk for developing pathologic changes. For this reason, increase in the thickness of the intima-media layers of carotid arteries can be a harbinger of coronary atherosclerosis and also a prognostic factor for cardiovascular accidents. In this study, we evaluated the status of carotid intima-media thickness (CIMT) in patients with ESRD on dialysis and analyzed its association with other risk factors for cardiovascular diseases. This cross-sectional study was conducted on patients referred for hemodialysis (HD) to the Taleghani Hospital (Shahid Beheshti University of Medical Sciences, Tehran, Iran) during 2007-2008. At the beginning, biochemical parameters and common cardiovascular risk factors were extracted from the patients' files, and then CIMT was measured by using B-Mode high-resolution ultrasonography, 1 cm proximal to the carotid bulb in the posterior wall. Finally, correlation between other risk factors and CIMT was made. One hundred patients with chronic and advanced renal disease were evaluated, including 46% females and 54% males. The mean age of these patients was 59.2 ± 13.1 years, with a range of 26-81 years. Correlations between CIMT and age (P = 0.023, r = 0.478), dialysis duration (P = 0.017, r = 0.435), number of cigarettes smoked (P = 0.026, r = 0.429), diastolic blood pressure (P = 0.013, r = 0.455) and fasting blood sugar (P = 0.045, r = 0.346) were significant. Risk factors for cardiovascular disease in patients on HD are of significant interest because of the high prevalence and frequency of the disease in this group of patients. However, in the present study, we were not able to find a very consistent and definite role for some risk factors in our patients. More studies are required to make clear the role of these factors in patients on HD.

HIS-Based Support of Follow-Up Documentation - Concept and Implementation for Clinical Studies.

OBJECTIVE: Follow-up data must be collected according to the protocol of each clinical study, i.e. at certain time points. Missing follow-up information is a critical problem and may impede or bias the analysis of study data and result in delays. Moreover, additional patient recruitment may be necessary due to incomplete follow-up data. Current electronic data capture (EDC) systems in clinical studies are usually separated from hospital information systems (HIS) and therefore can provide limited functionality to support clinical workflow. In two case studies, we assessed the feasibility of HIS-based support of follow-up documentation. METHODS: We have developed a data model and a HIS-based workflow to provide follow-up forms according to clinical study protocols. If a follow-up form was due, a database procedure created a follow-up event which was translated by a communication server into an HL7 message and transferred to the import interface of the clinical information system (CIS). This procedure generated the required follow-up form and enqueued a link to it in a work list of the relating study nurses and study physicians, respectively. RESULTS: A HIS-based follow-up system automatically generated follow-up forms as defined by a clinical study protocol. These forms were scheduled into work lists of study nurses and study physicians. This system was integrated into the clinical workflow of two clinical studies. In a study from nuclear medicine, each scenario from the test concept according to the protocol of the single photon emission computer tomography/computer tomography (SPECT/CT) study was simulated and each scenario passed the test. For a study in psychiatry, 128 follow-up forms were automatically generated within 27 weeks, on average five forms per week (maximum 12, minimum 1 form per week). CONCLUSION: HIS-based support of follow-up documentation in clinical studies is technically feasible and can support compliance with study protocols.

German disease management guidelines: surgical therapies for chronic heart failure.

The German Disease Management Guideline "Chronic Heart Failure" intends to guide physicians working in the field of diagnosis and treatment of heart failure. The guideline provides a tool on the background of evidence based medicine. The following short review wants to give insights into the role of some surgical treatment options to improve heart failure, such as revascularization, ventricular reconstruction and aneurysmectomy, mitral valve reconstruction, ventricular assist devices and heart transplantation.

Concept and Implementation of a Single Source Information System in Nuclear Medicine for Myocardial Scintigraphy (SPECT-CT data).

OBJECTIVE: Data for clinical documentation and medical research are usually managed in separate systems. We developed, implemented and assessed a documentation system for myocardial scintigraphy (SPECT/CT-data) in order to integrate clinical and research documentation. This paper presents concept, implementation and evaluation of this single source system including methods to improve data quality by plausibility checks. METHODS: We analyzed the documentation process for myocardial scintigraphy, especially for collecting medical history, symptoms and medication as well as stress and rest injection protocols. Corresponding electronic forms were implemented in our hospital information system (HIS) including plausibility checks to support correctness and completeness of data entry. Research data can be extracted from routine data by dedicated HIS reports. RESULTS: A single source system based on HIS-electronic documentation merges clinical and scientific documentation and thus avoids multiple documentation. Within nine months 495 patients were documented with our system by 8 physicians and 6 radiographers (466 medical history protocols, 466 stress and 414 rest injection protocols). Documentation consists of 295 attributes, three quarters are conditional items. Data quality improved substantially compared to previous paper-based documentation. CONCLUSION: A single source system to collect routine and research data for myocardial scintigraphy is feasible in a real-world setting and can generate high-quality data through online plausibility checks.

Multimodality molecular imaging--from target description to clinical studies.

This highlight lecture was presented at the closing session of the Annual Congress of the European Association of Nuclear Medicine (EANM) in Munich on 15 October 2008. The Congress was a great success: there were more than 4,000 participants, and 1,597 abstracts were submitted. Of these, 1,387 were accepted for oral or poster presentation, with a rejection rate of 14%. In this article a choice was made from 100 of the 500 lectures which received the highest scores by the scientific review panel. This article outlines the major findings and trends at the EANM 2008, and is only a brief summary of the large number of outstanding abstracts presented. Among the great number of oral and poster presentations covering nearly all fields of nuclear medicine some headlines have to be defined highlighting the development of nuclear medicine in the 21st century. This review focuses on the increasing impact of molecular and multimodality imaging in the field of nuclear medicine. In addition, the question may be asked as to whether the whole spectrum of nuclear medicine is nothing other than molecular imaging and therapy. Furthermore, molecular imaging will and has to go ahead to multimodality imaging. In view of this background the review was structured according to the single steps of molecular imaging, i.e. from target description to clinical studies. The following topics are addressed: targets, radiochemistry and radiopharmacy, devices and computer science, animals and preclinical evaluations, and patients and clinical evaluations.

Risk-profile and outcome of small papillary and follicular thyroid carcinomas (

AIM: According to the procedure guidelines of the German Society of Nuclear Medicine no radioiodine ablation is necessary in patients with papillary microcarcinomas in case of limited surgical resection. Few data are available with respect to the optimal management of patients with small follicular thyroid carcinomas. It was the aim to compare risk-profile and outcome of patients with small papillary (PTC) and follicular thyroid carcinomas (FTC)

[Hereditary angioneurotic edema. Treatment of a pseudosurgical digestive attack with C1 inhibitor concentrate]. / Oedème angioneurotique héréditaire. Traitement d'une crise digestive pseudo-chirurgicale par le C1-inhibiteur concentré.

Although anabolic androgens can be used to prevent acute attacks of hereditary angioneurotic oedema, these are still observed. When they are severe, and even more so when they involve the larynx or the abdominal viscera, an emergency treatment is necessary, ideally with the purified C1-inhibitor (C1-INH) administered by intravenous infusion. In a case with pseudo-surgical abdominal symptoms, this treatment was followed by an unusually dramatic regression of all symptoms. Serial laboratory examinations showed an increase in C1-INH and C2 plasma levels and in the number of basophils within less than 30 minutes; the increase in C4 levels occurred later. Thus, C1-INH is very effective in the treatment of acute hereditary angioneurotic oedema, but the product is not widely available; it should be reserved to severe forms affecting the larynx and the viscera.

[Idiopathic cyclic edema. The role of capillary hyperpermeability and its correction by Ginkgo biloba extract]. / Oedèmes cycliques idiopathiques. Rôle de l'hyperperméabilité capillaire et correction par extrait de Ginkgo biloba.

Idiopathic cyclic oedema is a frequent and often unrecognized condition in young women. It is characterized by water and sodium retention with secondary hyperaldosteronism due to capillary hyperpermeability. Treatment is not easy. It includes spironolactone, sometimes sympathomimetics and hygienic-dietetic measures. Thiazide diuretics and laxatives must be avoided. Correcting the capillary defect is of paramount importance. This defect is detected and measured by Landis' labelled albumin test. The authors have tried Ginkgo biloba extract administered either orally or by intravenous infusion. Full correction of the biological anomaly was obtained in 10 cases in which Landis' test was performed before and after oral treatment, and in the 5 cases treated by intravenous infusion.