Background To assess which parameters of [68Ga]Ga‐PSMA‐11 positron emission tomography (PSMA‐PET) predict response to systemic therapies in metastatic (m) castration‐resistant prostate cancer (CRPC). In addition, to investigate which of these factors are associated with overall survival (OS). Methods We retrospectively assessed the following PSMA‐PET parameters in 43 patients before and after systemic therapies for mCRPC: PSMA total tumor volume (TTV), mean standardized uptake value (SUVmean), SUVmax, and SUVpeak. prostate‐specific antigen (PSA) levels and PSMA‐PET/CT(magnetic resonance imaging [MRI]) imaging were both performed within 8 weeks before and 6 weeks after systemic therapy. PSMA‐PET and CT (MRI) images were reviewed according to the modified PET Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results were compared to PSA response. Univariable survival analyses were performed. Results Overall, 43 patients undergoing 67 systemic therapies were included (9 patients radium‐223, 12 cabazitaxel, 22 docetaxel, 6 abiraterone, and 18 enzalutamide). Median serum PSA level before any therapy was 11.3 ng/mL (interquartile range [IQR] = 3.3, 30.1). Delta (d) PSA after systemic therapies was −41%, dTTV 10.5%, dSUVmean −7.5%, dSUVmax −13.3%, dSUVpeak −12%, and dRECIST −13.3%. Overall, 31 patients had dPSA response (46.3%), 12 stable disease (17.9%), and 24 progressive disease (35.8%). All observed PET parameters, as well as the RECIST evaluation, were significantly associated with PSA response (dTTV P = .003, dSUVmean P = .003, dSUVmax P = .011, dSUVpeak P < 0001, dRECIST P = .012), while RECIST assessment was applicable in 37 out of 67 patients (55.2%). Within a median follow‐up of 33 months (IQR = 26, 38), 10 patients (23.3%) died of PC. On univariable survival analyses, neither the investigated PET parameters nor PSA level or RECIST criteria were associated with OS. Conclusion PSMA‐PET provides reliable parameters for prediction of response to systemic therapies for mCRPC. These parameters, if confirmed, could enhance RECIST criteria, specifically concerning its limitations for sclerotic bone lesions.
Dalbavancin is a new semisynthetic lipoglycopeptide with improved antimicrobial activity against various gram-positive pathogens. It demonstrates an extensive plasma half-life which permits outpatient parenteral antimicrobial therapy with weekly intervals and might therefore be an excellent treatment alternative for patients requiring prolonged antimicrobial therapy. The present study investigated dalbavancin monotherapy in an experimental implant-related methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis model. A clinical MRSA isolate and a Kirschner-wire were inserted into the proximal tibia of anaesthetized Sprague-Dawley rats. Four weeks after infection 34 animals were treated over 4 weeks with either dalbavancin (20 mg/kg loading-dose; 10 mg/kg daily), vancomycin (50 mg/kg twice daily) or left untreated. Twenty-four hours after the last treatment dose tibial bones and Kirschner-wires were harvested for microbiological examination. Based on quantitative bacterial cultures of osseous tissue, dalbavancin was as effective as vancomycin and both were superior to no treatment. No emergence of an induced glycopeptide-/lipoglycopeptide- resistance was observed after a treatment period of four weeks with either dalbavancin or vancomycin. In conclusion, monotherapy with dalbavancin was shown to be as effective as vancomycin for treatment of experimental implant-related MRSA osteomyelitis in rats, but both antimicrobials demonstrated only limited efficacy. Further studies are warranted to evaluate the clinical efficacy of dalbavancin for the treatment of periprosthetic S. aureus infections.
Purpose The goal of our study was comparison of external beam radiotherapy (EBRT) and I‑125 seeds brachytherapy in terms of biochemical control and development of late gastrointestinal and genitourinary side effects. Patients and methods 477 low-risk prostate cancer patients treated between 2000 and 2019 at our department using either I‑125 seeds brachytherapy or EBRT with a dose of 74 or 78 Gy were reviewed for our analysis. 213 patients were treated with EBRT and 264 with seeds. Results Patients were followed up yearly with a median follow-up of 70 (3–192) months. The biochemical no evidence of disease (bNED) rates after 5 years were 95% for both EBRT and seeds, and after 10 years 87% for EBRT and 94% for seeds using the Phoenix criteria, although no significant difference was observed. Concerning gastrointestinal side effects, EBRT showed significantly higher rates of RTOG grade ≥2 toxicity compared to seeds, but at no point in follow-up more than 15% of all patients. On the other hand, genitourinary side effects were significantly more prevalent in patients treated with seeds, with 40% RTOG grade ≥2 toxicity 12 months after treatment. Nevertheless, both types of side effects decreased over time. Conclusion Both EBRT and seeds provide excellent biochemical control with bNED rates after 10 years of about 90%. In terms of side effects, patients treated with seeds show higher grades of genitourinary side effects, while patients treated with EBRT show higher grades of gastrointestinal side effects.
Purpose of reviewTo give an overview of the most relevant recent literature about urinary tract infections (UTI) after radical cystectomy and to discuss them in the context of new individualized therapy approaches and possible preventive measures.Recent findingsUTI following radical cystectomy is a common complication associated with significant morbidity and readmission risk. Recent literature focuses on the identification of risk factors and the optimization of management. The risk factors most commonly associated with increased risk for UTI were perioperative blood transfusions and orthotopic neobladder (ONB). Furthermore, the effect of perioperative antibiotic regimens on rates of postoperative infections has been studied, but no consistent significant changes in UTI rates have yet been identified. Guidelines should be based on urologic studies and, wherever appropriate, should be uniform in design to encourage more frequent adherence. Furthermore, understanding the pathomechanisms leading to the development of UTI after radical cystectomy needs to be more central to discussions.SummaryUniform definition of UTI, characteristics of bacterial pathogens involved, and type and duration of antibiotics used and identification of clinical risk factors must be the focus of well designed prospective studies to enable reduction of the most common complication after radical cystectomy.
Purpose of reviewThe aim of this study was to give an overview of molecular alterations in upper tract urothelial carcinomas (UTUCs) and to discuss them in the context of current and prospective systemic therapies. Recent findingsUTUCs not only share a similar molecular landscape with urothelial carcinoma of the bladder (UCB), but also have distinct molecular features that can have an impact on therapy selection. FGFR3 alterations occur with a significant higher frequency in UTUC, with up to 40% of tumours harbouring FGFR3 driver mutations compared with 20% in UCB. In addition, a substantial number of high-grade UTUC show an immunedepleted phenotype and a luminal papillary expression subtype, thus predisposing them for FGFR inhibitor treatment. Approximately 20% of UTUC tumours have acquired mutations in TP53 and demonstrate a significant degree of genomic instability, which makes them candidates for systemic chemotherapy or immunotherapy. Whereas microsatellite instability (MSI) is rare in sporadic UTUC, 5-10% of UTUC patients have germline mutations in DNA mismatch repair genes, which leads to high MSI with enriched neoantigen load and presumably better response rates to immunotherapy. SummaryTreatment decisions in UTUC should take molecular tumour characteristics into account. The currently most therapy-relevant molecular alterations in UTUC comprise FGFR3 mutational status and mutations in DNA mismatch repair genes with concomitant microsatellite instability.
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