Refine
Has Fulltext
- yes (75)
Is part of the Bibliography
- yes (75)
Year of publication
Document Type
- Journal article (47)
- Doctoral Thesis (28)
Keywords
- prostate cancer (18)
- PSMA (6)
- Prostatakrebs (6)
- radioligand therapy (6)
- Prostatakarzinom (5)
- Nierenzellkarzinom (4)
- PET/CT (4)
- PSA (4)
- angiogenesis (4)
- biomarker (4)
- bladder cancer (4)
- miRNS (4)
- recurrence (4)
- Biomarker (3)
- Nierenkrebs (3)
- Renal cell carcinoma (3)
- cancer (3)
- miR-21 (3)
- miRNA (3)
- microRNA (3)
- microRNA-221 (3)
- progression (3)
- renal cell carcinoma (3)
- tumor microenvironment (3)
- Blasenkrebs (2)
- Harnableitung (2)
- Harnblasenkarzinom (2)
- Hypernephrom (2)
- Nephrektomie (2)
- PSMA I&T (2)
- Prostata (2)
- Prostatektomie (2)
- RCC (2)
- SOAT1 (2)
- Urologie (2)
- biomarkers (2)
- high-risk prostate cancer (2)
- immunotherapy (2)
- kidney cancer (2)
- machine learning (2)
- metastasis (2)
- miR (2)
- miR-126 (2)
- nephron sparing surgery (2)
- perineal (2)
- pouch (2)
- prognosis (2)
- proliferation (2)
- prostatectomy (2)
- radical prostatectomy (2)
- retropubic (2)
- risk stratification (2)
- surgery (2)
- --- (1)
- 68Ga-PSMA ligand PET/CT (1)
- Angiogenese (1)
- Angiostatin (1)
- Antiangiogenese (1)
- Assessment (1)
- BCG (1)
- BIRC7 (1)
- Bacillus-Calmette-Guerin (1)
- Bildgebendes Verfahren (1)
- Biopsy (1)
- Bub1b (1)
- Buccal mucosa graft (1)
- CCR7 (1)
- CD34 (1)
- COVID-19 (1)
- CTCAE (1)
- Cancer Cell (1)
- Carcinogenese (1)
- CpG island hypermethylation (1)
- DRE (1)
- DRU (1)
- Diagnostik (1)
- Docetaxel (1)
- Dünndarmblase (1)
- EAU guidelines (1)
- Ektomie (1)
- End-to-end-anastomosis (1)
- End-zu-End-Anastomose (1)
- Ereignisdatenanalyse (1)
- Erhaltungstherapie (1)
- Exenteration (1)
- Expressionsprofil (1)
- FDG (1)
- Fibroblasten (1)
- Frailty (1)
- GSTP1 (1)
- Gebrechlichkeit (1)
- Gebärmutterhalskrebs (1)
- Gemcitabin (1)
- Gen bub1b (1)
- Gen p53 (1)
- Genexpression (1)
- Geriatrie (1)
- Gleason Score (1)
- Gleason score (1)
- Gleason-System (1)
- Grading (1)
- Harnableitungsverfahren (1)
- Harnröhrenrekonstruktion (1)
- Harnröhrenstriktur (1)
- Harnröhrenverengung (1)
- Hemospermia (1)
- Hochrisikokarzinom der Prostata (1)
- IL-4 Rezeptor (1)
- IL-4 receptor (1)
- Ileozökalpouch (1)
- Ileum-Konduit (1)
- Index (1)
- Inferior vena cava (1)
- Interferon (1)
- Interferonsignal (1)
- Karzinom (1)
- Kidney cancer (1)
- Komorbiditäten (1)
- Kontinenz (1)
- Kontinenzplastik (1)
- LASP1 (1)
- LNCaP (1)
- Lebensqualität (1)
- MAD2 (1)
- MAINZPouch (1)
- MSI (1)
- MTB (1)
- Mamma (1)
- Marker (1)
- Medizin (1)
- Metastatic melanoma (1)
- Metformin (1)
- MicroRNA (1)
- MicroRNA-146b (1)
- Mikrosatelliteninstabilitäten (1)
- MircoRNA (1)
- Mundschleimhaut-Transplantation (1)
- N-Ras (1)
- NMIBC (1)
- Nierenfunktion (1)
- Nierentumor (1)
- Operation (1)
- Organerhalt (1)
- Outcome (1)
- Outcome lymphogen metastasierter Urothelkarzinome bladder transitional carcinoma lymph node involvement (1)
- PCa (1)
- PIK3R1 (1)
- PSA response (1)
- PSMA-617 (1)
- PSMA-RADS (1)
- PSMA-TV (1)
- PSMA‐617 (1)
- Partin Tables (1)
- Profiling (1)
- Prognosefaktor (1)
- Prognosis (1)
- Prostata-spezifisches Antigen (1)
- Prostatabiopsie (1)
- Prostatacarzinom (1)
- Prostatakarzinome (1)
- Prostatastanzbiopsie (1)
- RLT (1)
- Reconstruction of the urethra (1)
- Renal Cell Carcinoma (1)
- Retropubische Prostatektomie (1)
- SARS-CoV-2 (1)
- SOCS-3 (1)
- SP-fixation (1)
- SUV (1)
- Screening (1)
- Seminal vesicle tumor (1)
- Spindelapparat (1)
- Spindlecheckpoint (1)
- Stricture of the urethra (1)
- Sunitinib (1)
- T1 (1)
- TKI (1)
- TRAIL (1)
- TRUS (1)
- Teilresektion (1)
- Thrombectomy (1)
- Tumor thrombus (1)
- Tumorgenese (1)
- Tumorneoangiogenese (1)
- Tumorsuppressor (1)
- Tumour markers (1)
- Tyrosine kinase inhibition (1)
- UMAP (1)
- Ultrasound (1)
- Ureterimplantation (1)
- Urin (1)
- Urothelkarzinom (1)
- VEGF (1)
- Zellzyklus (1)
- Zystektomie (1)
- [177Lu]Lu-PSMA I&T (1)
- \(^{177}\)Lu (1)
- \(^{18}\)F-PSMA-1007 (1)
- adjuvant hormonal treatment (1)
- adrenal tumor (1)
- adrenal tumors (1)
- adrenocortical cancer (1)
- adrenocortical carcinoma (1)
- age (1)
- agreement (1)
- androgen deprivation therapy (1)
- angiogenesis inhibitors (1)
- angiostatin (1)
- antiangiogenesis (1)
- aplastic anemia (1)
- aquaporin 3 protein (1)
- bacillus calmette guerin (1)
- biomarkers UPA (1)
- bone marrow failure (1)
- bone marrow immune-microenvironment (1)
- breast carcinoma (1)
- cable-clamp implants (1)
- cancer care (1)
- cancer surveillance (1)
- caspase-3 (1)
- chemokine receptor (1)
- cholesterol metabolism (1)
- clinical trials (1)
- comparability (1)
- continence (1)
- continence mechanism (1)
- continent cutaneous urinary diversion (1)
- controlled clinical-trials (1)
- cystectomy (1)
- cytopenia (1)
- detection rate (1)
- diagnosis (1)
- digital-rektale Untersuchung (1)
- disorder of immunity (1)
- expression (1)
- expression profile (1)
- flare phenomenon (1)
- follow up (1)
- forecasting (1)
- gastric cancer (1)
- gene (1)
- gene expression (1)
- gene targeting (1)
- gesundheitsbezogene (1)
- growth (1)
- health-related (1)
- hematopoietic stem cells (1)
- hematotoxicity (1)
- high-risk Prostate Cancer (1)
- imaging diagnostics (1)
- immune infiltration (1)
- immune response (1)
- immune-checkpoint inhibitor (1)
- immunohistochemistry (1)
- in vitro (1)
- inhibitor PAI-1 (1)
- journals (1)
- kidney neoplasms (1)
- kidneys (1)
- late response (1)
- lipid metabolism (1)
- livin (1)
- localized tumor stages (1)
- luciferase (1)
- lymph node dissection (1)
- mRNA (1)
- mTOR (1)
- matched pair (1)
- metabolic tumour volume (MTV) (1)
- miR-145 (1)
- miR-200b (1)
- miR-205 (1)
- miR-221 (1)
- miR-221-5p (1)
- miR-29c (1)
- miRNAs (1)
- microarrays (1)
- microrna (1)
- microsatellite instability (1)
- migration (1)
- mir-203 (1)
- mitochondrial DNA (1)
- molecular subtypes (1)
- mtDNA (1)
- multiple myeloma (1)
- muscle-invasive bladder cancer (1)
- nephrotoxicity (1)
- oncogenes (1)
- organerhaltende Nierentumorchirurgie (1)
- outcomes research (1)
- outreach (1)
- overall survival (1)
- pT1-Stadien (1)
- pan-RCC (1)
- partin tables (1)
- pathological staging (1)
- patient access (1)
- patient outcome (1)
- pelvic exenteration (1)
- perivesical extension (1)
- positive lymph node (1)
- potential marker (1)
- precision medicine (1)
- precision oncology (1)
- prediction (1)
- predictive factors (1)
- preoperative patient selection (1)
- primary breast cancer (1)
- prognostic factor (1)
- prognostic-biomarkers (1)
- promoter methylation (1)
- prostate adenocarcinoma (1)
- prostate-specific membrane antigen (1)
- prostate-specific membrane antigen (PSMA) (1)
- prostatic neoplasms (1)
- protein biomarkers (1)
- präoperative Patientenselektion (1)
- pubic symphysis (1)
- quality of life (1)
- radical cystectomy (1)
- radical nephrectomy (1)
- radikal (1)
- randomized controlled trial (1)
- real cell cancer (1)
- real world data (1)
- receptor beta (1)
- receptor splice variant (1)
- recurrent prostate cancer (1)
- regression analysis (1)
- renal cancer (1)
- renal cel carcinoma (1)
- response (1)
- retropubisch (1)
- reveals (1)
- revisional surgery (1)
- salvage radiotherapy (1)
- software (1)
- spindle assembly checkpoint (1)
- stage pT1 (1)
- staging (1)
- standardized reporting system (1)
- surgical and invasive medical procedures (1)
- surgical oncology (1)
- survival (1)
- system bcg (1)
- t-SNE (1)
- taxane (1)
- testicular neoplasms (1)
- theranostics (1)
- total lesion PSMA (1)
- transcriptome (1)
- transcriptomic analysis (1)
- transitional cell carcinoma (1)
- transrektaler Ultraschall (1)
- tumor (1)
- tumor cells (1)
- tumor invasion front (1)
- tumor necrosis factor (1)
- tumor suppressor miRNA (1)
- tumor tissue (1)
- tumourneoangiogenesis (1)
- ubiquitin (1)
- update (1)
- urinary bladder neoplasms (1)
- urinary diversion (1)
- urine (1)
- urothelial bladder carcinoma (1)
- venous infiltration (1)
- visual clustering (1)
- water channels (1)
Institute
- Urologische Klinik und Poliklinik (75) (remove)
Sonstige beteiligte Institutionen
Prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) is increasingly utilized for staging of men with prostate cancer (PC). To increase interpretive certainty, the standardized PSMA reporting and data system (RADS) has been proposed. Using PSMA-RADS, we characterized lesions in 18 patients imaged with \(^{18}\)F-PSMA-1007 PET/CT for primary staging and determined the stability of semi-quantitative parameters. Six hundred twenty-three lesions were categorized according to PSMA-RADS and manually segmented. In this context, PSMA-RADS-3A (soft-tissue) or -3B (bone) lesions are defined as being indeterminate for the presence of PC. For PMSA-RADS-4 and -5 lesions; however, PC is highly likely or almost certainly present [with further distinction based on absence (PSMA-RADS-4) or presence (PSMA-RADS-5) of correlative findings on CT]. Standardized uptake values (SUV\(_{max}\), SUV\(_{peak}\), SUV\(_{mean}\)) were recorded, and volumetric parameters [PSMA-derived tumor volume (PSMA-TV); total lesion PSMA (TL-PSMA)] were determined using different maximum intensity thresholds (MIT) (40 vs. 45 vs. 50%). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories (p ≤ 0.0322). In particular, the clinically challenging PSMA-RADS-3A lesions showed significantly lower SUV\(_{max}\) and SUV\(_{peak}\) compared to the entire PSMA-RADS-4 or -5 cohort (p < 0.0001), while for PSMA-RADS-3B this only applies when compared to the entire PSMA-RADS-5 cohort (p < 0.0001), but not to the PSMA-RADS-4 cohort (SUV\(_{max}\), p = 0.07; SUV\(_{peak}\), p = 0.08). SUV\(_{mean}\) (p = 0.30) and TL-PSMA (p = 0.16) in PSMA-RADS-5 lesions were not influenced by changing the MIT, while PSMA-TV showed significant differences when comparing 40 vs. 50% MIT (p = 0.0066), which was driven by lymph nodes (p = 0.0239), but not bone lesions (p = 0.15). SUV\(_{max}\) was significantly higher in PSMA-RADS-5 lesions compared to all other PSMA-RADS categories in \(^{18}\)F-PSMA-1007 PET/CT. As such, the latter parameter may assist the interpreting molecular imaging specialist in assigning the correct PSMA-RADS score to sites of disease, thereby increasing diagnostic certainty. In addition, changes of the MIT in PSMA-RADS-5 lesions had no significant impact on SUV\(_{mean}\) and TL-PSMA in contrast to PSMA-TV.
Simple Summary
The calculation of PSMA-positive tumor volume (PSMA-TV) of the whole body from PSMA PET scans for response evaluation remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative tumor lesions. Changes in the whole-body PSMA-TV of 65 patients were comparable to the changes in PSMA-TV after including only the ten largest lesions. Moreover, changes in PSMA-TV correlated well with changes in PSA levels, as did the changes in PSMA-TV with the reduced number of lesions. We conclude that a response assessment using PSMA-TV with a reduced number of lesions is feasible and could lead to a simplified process for evaluating PSMA PET/CT.
Abstract
(1) Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET)-derived parameters, such as the commonly used standardized uptake value (SUV) and PSMA-positive tumor volume (PSMA-TV), have been proposed for response assessment in metastatic prostate cancer (PCa) patients. However, the calculation of whole-body PSMA-TV remains a time-consuming procedure. We hypothesized that it may be possible to quantify changes in PSMA-TV by considering only a limited number of representative lesions. (2) Methods: Sixty-five patients classified into different disease stages were assessed by PSMA PET/CT for staging and restaging after therapy. Whole-body PSMA-TV and whole-body SUV\(_{max}\) were calculated. We then repeated this calculation only including the five or ten hottest or largest lesions. The corresponding serum levels of prostate-specific antigen (PSA) were also determined. The derived delta between baseline and follow-up values provided the following parameters: ΔSUV\(_{maxall}\), ΔSUV\(_{max10}\), ΔSUV\(_{max5}\), ΔPSMA-TV\(_{all}\), ΔPSMA-TV\(_{10}\), ΔPSMA-TV\(_{5}\), ΔPSA. Finally, we compared the findings from our whole-body segmentation with the results from our keyhole approach (focusing on a limited number of lesions) and correlated all values with the biochemical response (ΔPSA). (3) Results: Among patients with metastatic hormone-sensitive PCa (mHSPC), none showed a relevant deviation for ΔSUV\(_{max10}\)/ΔSUV\(_{max5}\) or ΔPSMA-TV\(_{10}\)/ΔPSMA-TV\(_{5}\) compared to ΔSUV\(_{maxall}\) and ΔPSMA-TV\(_{all}\). For patients treated with taxanes, up to 6/21 (28.6%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only up to 2/21 (9.5%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). For patients treated with radioligand therapy (RLT), up to 5/28 (17.9%) showed clinically relevant deviations between ΔSUV\(_{maxall}\) and ΔSUV\(_{max10}\) or ΔSUV\(_{max5}\), but only 1/28 (3.6%) patients showed clinically relevant deviations between ΔPSMA-TV\(_{all}\) and ΔPSMA-TV\(_{10}\) or ΔPSMA-TV\(_{5}\). The highest correlations with ΔPSA were found for ΔPSMA-TV\(_{all}\) (r ≥ 0.59, p ≤ 0.01), followed by ΔPSMA-TV\(_{10}\) (r ≥ 0.57, p ≤ 0.01) and ΔPSMA-TV\(_{5}\) (r ≥ 0.53, p ≤ 0.02) in all cohorts. ΔPSA only correlated with ΔSUV\(_{maxall}\) (r = 0.60, p = 0.02) and with ΔSUV\(_{max10}\) (r = 0.53, p = 0.03) in the mHSPC cohort, as well as with ΔSUV\(_{maxall}\) (r = 0.51, p = 0.01) in the RLT cohort. (4) Conclusion: Response assessment using PSMA-TV with a reduced number of lesions is feasible, and may allow for a simplified evaluation process for PSMA PET/CT.
Die miR-200b zeigte sich in zwei unabhängigen Prostatakarzinomkollektiven herabreguliert und in dem verwendeten Hochrisiko Kollektiv erwies sich miR-200b zudem in uni- und multivariaten Analysen in einem retrospektiven Versuchsansatz als geeigneter Marker zur Abschätzung der Prognose des Prostatakarzinoms. Mittels in vitro Experimenten konnten tumorsuppressive Funktionen von miR-200b bestätigt werden, da miR-200b überexprimierende Prostatakarzinom Zelllinien eine geringere Proliferation und eine geringere Autophagie zeigten. Zusätzlich konnte auf funktioneller Ebene, SOAT1 als Zielgen von miR-200b definiert werden. Die funktionelle Bedeutung der miR-200b vermittelten Regulation der SOAT1 Expression konnte in weiteren Experimenten bestätigt werden, indem eine Sensitivierung gegenüber der antiproliferativen Wirkung von SOAT1 Inhibitoren in miR-200b überexprimierenden Prostatakarzinom-Zellen beobachtet werden konnte. Mit diesen Ergebnissen konnte ein Model entwickelt werden, welches einen möglichen Erklärungsansatz der Bedeutung, der von miR-200b vermittelten SOAT1 Regulation für den Fettstoffwechsel des Prostatakarzinoms liefern könnte.
Das Urothelkarzinom ist das zweithäufigste urologische Malignom mit weltweit steigender Inzidenz. Nach initial kurativ intendierter transurethraler Resektion des Tumors zeigt bislang immer noch jeder vierte Patient einen Progress im Verlauf mit einem erhöhten Risiko einer Metastasierung, ohne dass hierfür verlässliche prognostische Marker zur Verfügung stehen. Mithilfe eines solchen (Bio)markers könnte beim Urothelkarzinom eine frühzeitige Diagnostik von Hochrisikokarzinomen ermöglicht, die Therapieplanung verbessert und somit das Risiko einer Metastasierung und erhöhten Mortalität gesenkt werden. Als mögliche Biomarker rücken micro-RNAs über ihre posttranskriptionelle Regulierung in den Fokus onkologischer Forschung. Mithilfe einer Datenbankrecherche wurden 7 verschiedene micro-RNAs (miR-9, -21, -29c, -145, -200c, -205, -221) selektioniert, welchen bereits in unterschiedlichen Malignomen eine Rolle in der Karzinogenese nachgewiesen werden konnte. Ein Einfluss dieser miRs im Urothelkarzinom war bislang noch nicht suffizient beschrieben, sodass anhand einer Expressionsanalyse in der vorliegenden Arbeit ein Biomarker für einen Progress untersucht werden sollte. Hierfür wurde ein archiviertes Gewebekollektiv, bestehend aus NMIBC, MIBC und benignem Referenzmaterial verwendet und die mittels RT-PCR ermittelte miR-Expression mit klinischen Parametern sowie Follow-up-Daten korreliert.
Letztlich konnte für unterschiedliche micro-RNAs ein Einfluss auf das Urothelkarzinom im untersuchten Kollektiv nachgewiesen werden und somit deren Bedeutung als Onko-miRs im Urothelkarzinom gestärkt werden. Aufbauend auf diesen Ergebnissen wurden die NMIBC retrospektiv anhand der Follow-up-Daten in zwei prognostisch unterschiedliche Subgruppen unterteilt und die Expressionsdaten miteinander verglichen. Es konnte gezeigt werden, dass sowohl miR-29c als auch miR-145 in prognostisch ungünstigeren NMIBC mit einem muskelinvasiven Rezidiv im Verlauf eine signifikant niedrigere Expression im untersuchten Kollektiv aufwiesen. Anhand eines in der Regressionsanalyse ermittelten Schwellenwertes konnte in der Kaplan-Meier-Analyse sowohl ein erhöhtes progressionsfreies Überleben als auch eine niedrigere tumorassoziierte Mortalität in den NMIBC mit einer miR-Expression unterhalb des ermittelten Schwellenwertes gezeigt werden. Somit wurde im untersuchten Kollektiv ein Marker ermittelt, welcher anhand der miR-29c und -145-Expression eine Unterteilung in prognostisch günstige und ungünstige Gruppen ermöglicht. In einem zweiten unabhängigen Validierungskollektiv wurden miR-29c und -145 auf ihre zuvor erhobene prognostische Aussagekraft untersucht. Hierbei konnte miR-145 als prognoserelevanter Biomarker nicht validiert werden. Für miR-29c konnte hingegen erneut eine niedrige Expression mit einer schlechteren klinischen Prognose assoziiert werden. Zudem konnte der zuvor ermittelte Schwellenwert auch in dem zweiten Kollektiv und miR-29c somit als Prognosemarker in den untersuchten Kollektiven validiert werden.
In der Zellkultur konnte die tumorsuppressive Funktion der miR-29c weiter bestätigt werden. So zeigte sich in ektopisch miR-29c-überexprimierten Urothelkarzinomzellen eine signifikant niedrigere Proliferations- und Migrationsrate. Um die posttranskriptionelle Funktion der tumorsuppressiven miR-29c weiter abzuklären, konnte LOXL2 als ein solides Zielgen der miR-29c mittels RT-PCR-Analysen identifiziert werden.
Anhand dieser Ergebnisse konnten vor allem miR-29c tumorsuppressive Eigenschaften im Urothelkarzinom zugeschrieben werden. Im untersuchten Gewebekollektiv stellt die miR-29c einen relevanten Progressionsmarker dar, welcher im Rahmen prospektiver Studien weiter validiert werden könnte. Eine Implementierung der miR-29c-Expressionsanalyse in die Diagnostik der NMIBC ist somit insgesamt ein vielversprechender Ansatz um eine rasche Diagnose von Hochrisikokarzinomen zu stellen und folglich einer frühzeitigen Therapie zugänglich zu machen.
Personalized oncology is a rapidly evolving area and offers cancer patients therapy options that are more specific than ever. However, there is still a lack of understanding regarding transcriptomic similarities or differences of metastases and corresponding primary sites. Applying two unsupervised dimension reduction methods (t-Distributed Stochastic Neighbor Embedding (t-SNE) and Uniform Manifold Approximation and Projection (UMAP)) on three datasets of metastases (n = 682 samples) with three different data transformations (unprocessed, log10 as well as log10 + 1 transformed values), we visualized potential underlying clusters. Additionally, we analyzed two datasets (n = 616 samples) containing metastases and primary tumors of one entity, to point out potential familiarities. Using these methods, no tight link between the site of resection and cluster formation outcome could be demonstrated, or for datasets consisting of solely metastasis or mixed datasets. Instead, dimension reduction methods and data transformation significantly impacted visual clustering results. Our findings strongly suggest data transformation to be considered as another key element in the interpretation of visual clustering approaches along with initialization and different parameters. Furthermore, the results highlight the need for a more thorough examination of parameters used in the analysis of clusters.
(1) Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) has shown remarkable results in patients with advanced prostate cancer. We aimed to evaluate the toxicity profile of the PSMA ligand [\(^{177}\)Lu]Lu-PSMA I&T. (2) Methods: 49 patients with metastatic, castration-resistant prostate cancer treated with at least three cycles of [\(^{177}\)Lu]Lu-PSMA I&T were evaluated. Prior to and after RLT, we compared leukocytes, hemoglobin, platelet counts, and renal functional parameters (creatinine, eGFR, n = 49; [\(^{99m}\)Tc]-MAG3-derived tubular extraction rate (TER), n = 42). Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 and KDIGO Society. To identify predictive factors, we used Spearman's rank correlation coefficient. (3) Results: A substantial fraction of the patients already showed impaired renal function and reduced leukocyte counts at baseline. Under RLT, 11/49 (22%) patients presented with nephrotoxicity CTCAE I or II according to creatinine, but 33/49 (67%) according to eGFR. Only 5/42 (13%) showed reduced TER, defined as <70% of the age-adjusted mean normal values. Of all renal functional parameters, absolute changes of only 2% were recorded. CTCAE-based re-categorization was infrequent, with creatinine worsening from I to II in 2/49 (4.1%; GFR, 1/49 (2%)). Similar results were recorded for KDIGO (G2 to G3a, 1/49 (2%); G3a to G3b, 2/49 (4.1%)). After three cycles, follow-up eGFR correlated negatively with age (r = −0.40, p = 0.005) and the eGFR change with Gleason score (r = −0.35, p < 0.05) at baseline. Leukocytopenia CTCAE II occurred only in 1/49 (2%) (CTCAE I, 20/49 (41%)) and CTCAE I thrombocytopenia in 7/49 (14%), with an absolute decrease of 15.2% and 16.6% for leukocyte and platelet counts. Anemia CTCAE II occurred in 10/49 (20%) (CTCAE I, 36/49 (73%)) with a decrease in hemoglobin of 4.7%. (4) Conclusions: After PSMA-targeted therapy using [\(^{177}\)Lu]Lu-PSMA I&T, no severe (CTCAE III/IV) toxicities occurred, thereby demonstrating that serious adverse renal or hematological events are unlikely to be a frequent phenomenon with this agent.
In recent years, it has become increasingly apparent that bone marrow (BM) failures and myeloid malignancy predisposition syndromes are characterized by a wide phenotypic spectrum and that these diseases must be considered in the differential diagnosis of children and adults with unexplained hematopoiesis defects. Clinically, hypocellular BM failure still represents a challenge in pathobiology-guided treatment. There are three fundamental topics that emerged from our review of the existing data. An exogenous stressor, an immune defect, and a constitutional genetic defect fuel a vicious cycle of hematopoietic stem cells, immune niches, and stroma compartments. A wide phenotypic spectrum exists for inherited and acquired BM failures and predispositions to myeloid malignancies. In order to effectively manage patients, it is crucial to establish the right diagnosis. New theragnostic windows can be revealed by exploring BM failure pathomechanisms.
(1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in Würzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities; (3) Results: the highest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed for identifying so-called white spots—regions within our catchment that were relatively underrepresented in WERA MTBs; (4) Conclusions: investigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in providing precision oncology and help establishing a joint WERA-wide outreach strategy.
Background
Radioligand therapy (RLT) with \(^{177}\)Lu-labeled prostate-specific membrane antigen (PSMA) ligands is associated with prolonged overall survival (OS) in patients with advanced, metastatic castration-resistant prostate cancer (mCRPC). A substantial number of patients, however, are prone to treatment failure. We aimed to determine clinical baseline characteristics to predict OS in patients receiving [\(^{177}\)Lu]Lu-PSMA I&T RLT in a long-term follow-up.
Materials and methods
Ninety-two mCRPC patients treated with [\(^{177}\)Lu]Lu-PSMA I&T with a follow-up of at least 18 months were retrospectively identified. Multivariable Cox regression analyses were performed for various baseline characteristics, including laboratory values, Gleason score, age, prior therapies, and time interval between initial diagnosis and first treatment cycle (interval\(_{Diagnosis-RLT}\), per 12 months). Cutoff values for significant predictors were determined using receiver operating characteristic (ROC) analysis. ROC-derived thresholds were then applied to Kaplan–Meier analyses.
Results
Baseline C-reactive protein (CRP; hazard ratio [HR], 1.10, 95% CI 1.02–1.18; P = 0.01), lactate dehydrogenase (LDH; HR, 1.07, 95% CI 1.01–1.11; P = 0.01), aspartate aminotransferase (AST; HR, 1.16, 95% CI 1.06–1.26; P = 0.001), and interval\(_{Diagnosis-RLT}\) (HR, 0.95, 95% CI 0.91–0.99; P = 0.02) were identified as independent prognostic factors for OS. The following respective ROC-based thresholds were determined: CRP, 0.98 mg/dl (area under the curve [AUC], 0.80); LDH, 276.5 U/l (AUC, 0.83); AST, 26.95 U/l (AUC, 0.73); and interval\(_{Diagnosis-RLT}\), 43.5 months (AUC, 0.68; P < 0.01, respectively). Respective Kaplan–Meier analyses demonstrated a significantly longer median OS of patients with lower CRP, lower LDH, and lower AST, as well as prolonged interval\(_{Diagnosis-RLT}\) (P ≤ 0.01, respectively).
Conclusion
In mCRPC patients treated with [\(^{177}\)Lu]Lu-PSMA I&T, baseline CRP, LDH, AST, and time interval until RLT initiation (thereby reflecting a possible indicator for tumor aggressiveness) are independently associated with survival. Our findings are in line with previous findings on [\(^{177}\)Lu]Lu-PSMA-617, and we believe that these clinical baseline characteristics may support the nuclear medicine specialist to identify long-term survivors.