Search

Upregulation of prostate-specific membrane antigen (PSMA) in neovasculature has been described in glioblastoma multiforme (GBM), whereas vasculature in nonaffected brain shows hardly any expression of PSMA. It is unclear whether PSMA-targeting tracer uptake on PET is based on PSMA-specific binding to neovasculature or aspecific uptake in tumor. Here, we quantified uptake of various PSMA-targeting tracers in GBM and correlated this with PSMA expression in tumor biopsy samples from the same patients. Methods: Fourteen patients diagnosed with de novo ( n = 8) or recurrent ( n = 6) GBM underwent a preoperative PET scan after injection of 1.5 MBq/kg [ 68 Ga]Ga-PSMA-11 ( n = 7), 200 MBq of [ 18 F]DCFpyl ( n = 3), or 200 MBq of [ 18 F]PSMA-1007 ( n = 4). Uptake in tumor and tumor-to-background ratios, with contralateral nonaffected brain as background, were determined. In a subset of patients, PSMA expression levels from different regions in the tumor tissue samples ( n = 40), determined using immunohistochemistry ( n = 35) or RNA sequencing ( n = 13), were correlated with tracer uptake on PET. Results: Moderate to high (SUV max , 1.3-20.0) heterogeneous uptake was found in all tumors irrespective of the tracer type used. Uptake in nonaffected brain was low, resulting in high tumor-to-background ratios (6.1-359.0) calculated by dividing SUV max of tumor by SUV max of background. Immunohistochemistry showed variable PSMA expression on endothelial cells of tumor microvasculature, as well as on dispersed individual cells (of unknown origin), and granular staining of the neuropil. No correlation was found between in vivo uptake and PSMA expression levels (for immunohistochemistry, r = -0.173, P = 0.320; for RNA, r = -0.033, P = 0.915). Conclusion: Our results indicate the potential use of various PSMA-targeting tracers in GBM. However, we found no correlation between PSMA expression levels on immunohistochemistry and uptake intensity on PET. Whether this may be explained by methodologic reasons, such as the inability to measure functionally active PSMA with immunohistochemistry, tracer pharmacokinetics, or the contribution of a disturbed blood-brain barrier to tracer retention, should still be investigated., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Older patients (> 65 yr) suffering from overactive bladder (OAB) are more likely to have functional impairment and comorbidity than those without OAB. This article reviews available published studies and discusses how fesoterodine might meet the specific needs of the older OAB patient., Methods: A comprehensive literature search was undertaken in order to evaluate fesoterodine safety in older OAB patients., Results: Fesoterodine offers flexible dosing, allowing the clinician to balance risk and benefits according to the symptoms and preferences of the patient. Its balanced affinity for M2 and M3 muscarinic receptors may lead to its benefit on OAB symptoms. Its active metabolite is a P-gp substrate that is actively transported from the central nervous system (CNS), potentially avoiding adverse CNS effects. Fesoterodine can be used in mild or moderate hepatic or renal insufficiency and no dose adjustment is routinely required. Fesoterodine's benefit has been demonstrated in multiple clinical trials in older and medically vulnerable patients. Fesoterodine was rated as "beneficial" in the LUTS-FORTA classification due to its efficiency and tolerability in older patients., Conclusion: Here, the use of fesoterodine in older and vulnerable patients is summarized given the need to approach pharmacotherapy for OAB differently in older adults., Competing Interests: CONFLICT OF INTEREST DISCLOSURES We have read and understood the Canadian Geriatrics Journal’s policy on conflicts of interest disclosure. J. Heesakkers has received support as a consultant/lecturer from Astellas, Allergan, Bluewind, UrogynBV, and Pierre Fabre, and for scientific studies and trials from Astellas, Boston Scientific, Ipsen, Bluewind, and UrogynBV. M. te Dorsthorst has received an unrestricted grant from Bluewind. A. Wagg has received honoraria from Astellas as a speaker and for consulting; from Essity Health & Hygiene AB for consulting, research and as a speaker; from Pfizer Corporation for consulting and research grants; and honoraria from Pierre Fabre as a speaker., (© 2022 Author(s). Published by the Canadian Geriatrics Society.)

Purpose: The aim of this study was to demonstrate features predictive of treatment response for patient-tailored overactive bladder (OAB) intervention with an implantable tibial neurostimulator using patient and technical prediction factors., Materials and Methods: This study was designed as a follow-up study based on parameter settings and patients' preferences during the pilot and extended study of the implantable tibial nerve stimulator (RENOVA™ iStim system). For this study, we compared all treatment parameters (stimulation amplitude, frequency, and pulse width) and usage data (duration of treatment) during the different follow-up visits., Results: We obtained usage data from a total of 32 patients who were implanted with the system between February and September 2015. Age, sex, body mass index (BMI) and previous experience with percutaneous tibial nerve stimulation (PTNS) treatment were considered as possible prediction factors for treatment success. However, only BMI was considered a statistically significant prediction factor (p = 0.042). A statistically significant increase in mean treatment level was seen in the responder group during the 3 month follow-up visit (mean: 6.7 mA, SD 0.416) as compared with the initial system activation visit (mean: 5.8 mA, SD 0.400) (p = 0.049). No other visits demonstrated statistically significant changes in both groups (responders and nonresponders) during the defined timepoints., Conclusion: This data underscores the need to use patient-tailored OAB treatment. BMI was found to be a negative predictive factor for treatment success. However, it was not possible to develop a specific responder model. A model predicting response to treatment could be useful for implementing shared decision making., (© 2022 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Introduction and Objectives: Overactive bladder syndrome (OAB) is defined as urinary urgency, with or without urgent urinary incontinence; it is often associated with urinary frequency and nocturia, in the absence of any pathological or metabolic conditions that may cause or mimic OAB. The aim of this study was to evaluate the long-term real-life adherence of transcutaneous tibial nerve stimulation (TTNS) in the treatment of OAB, patient satisfaction of the treatment, and reasons for quitting therapy., Materials and Methods: In this single center study, all patients who had a positive effect on percutaneous tibial nerve stimulation (PTNS) and continued to receive home-based treatment with TTNS since 2012 were included for analysis. Patients were retrospectively asked to fill out a questionnaire regarding satisfaction, reasons for quitting, and additional or next line of therapy., Results: We included 42 patients for this study, 81% of these patients were female ( n  = 34). The median age was 67 years (range 36-86). Most of the patients (64%, n  = 27) were diagnosed with OAB wet. The median TTNS treatment persistence was 16 months (range 1-112 months). Reasons and percentages for stopping therapy were: 55% stopped treatment due to loss of effect, and 24% stopped because of preferring other type of neuromodulation. The mean satisfaction score (scale 1-10) in patients who continued TTNS was 6.2 ( n  = 9, SD 1.30) versus 5.4 ( n  = 29, SD 2.24) for patients who quit therapy. We did not find a statistically significant difference between the two groups ( p  = 0.174)., Conclusion: TTNS, although effective in the short-term, is not effective in the long-term. In combination with a low satisfaction rate among patients, there is a need for improvement in terms of OAB treatment modalities., Competing Interests: Conflict of interest statement: Manon te Dorsthorst: Participation in the OASIS-trial, regarding the RENOVA implantable stimulation device for Tibial Nerve Stimulation (Firm: Bluewind) Dick Janssen: no conflict of interest. Frank Martens: Participation in the OASIS-trial, regarding the RENOVA implantable stimulation device for Tibial Nerve Stimulation (Firm: Bluewind) Michael van Balken: Participation in the OASIS-trial, regarding the RENOVA implantable stimulation device for Tibial Nerve Stimulation (Firm: Bluewind) John Heesakkers: Participation in the OASIS-trial, regarding the RENOVA implantable stimulation device for Tibial Nerve Stimulation (Firm: Bluewind), (© The Author(s), 2021.)

Glioblastoma (GBM) is the most malignant primary brain tumor for which no curative treatment options exist. Non-invasive qualitative (Visually Accessible Rembrandt Images (VASARI)) and quantitative (radiomics) imaging features to predict prognosis and clinically relevant markers for GBM patients are needed to guide clinicians. A retrospective analysis of GBM patients in two neuro-oncology centers was conducted. The multimodal Cox-regression model to predict overall survival (OS) was developed using clinical features with VASARI and radiomics features in isocitrate dehydrogenase ( IDH )-wild type GBM. Predictive models for IDH -mutation, 06-methylguanine-DNA-methyltransferase ( MGMT )-methylation and epidermal growth factor receptor ( EGFR ) amplification using imaging features were developed using machine learning. The performance of the prognostic model improved upon addition of clinical, VASARI and radiomics features, for which the combined model performed best. This could be reproduced after external validation (C-index 0.711 95% CI 0.64-0.78) and used to stratify Kaplan-Meijer curves in two survival groups ( p -value < 0.001). The predictive models performed significantly in the external validation for EGFR amplification (area-under-the-curve (AUC) 0.707, 95% CI 0.582-8.25) and MGMT -methylation (AUC 0.667, 95% CI 0.522-0.82) but not for IDH -mutation (AUC 0.695, 95% CI 0.436-0.927). The integrated clinical and imaging prognostic model was shown to be robust and of potential clinical relevance. The prediction of molecular markers showed promising results in the training set but could not be validated after external validation in a clinically relevant manner. Overall, these results show the potential of combining clinical features with imaging features for prognostic and predictive models in GBM, but further optimization and larger prospective studies are warranted.

Purpose of Review: Overactive bladder syndrome (OAB) is a chronic condition, which can be treated by tibial nerve stimulation. The present review will focus on the technical aspects, advantages, drawbacks, and limitations of the latest available applications of posterior tibial nerve stimulation., Recent Findings: We describe the technical aspects of recent developed implants and techniques of tibial nerve stimulation in a transcutaneous, percutaneous, and minimal invasive way. All different treatment options have advantages and disadvantages based on type of surgery, energy transfer, impedance, treatment setting options, risk of migration, and patient usability, which are described in this review. Only devices with data that are publicly available were included., Summary: New technologies are on their way in the field of tibial nerve stimulation for the treatment of OAB. Technical aspects are important to demonstrate safety and efficacy and user friendliness in order to obtain high acceptance of the various devices.

Many biology-based precision drugs are available that neutralize aberrant molecular pathways in cancer. Molecular heterogeneity and the lack of reliable companion diagnostic biomarkers for many drugs makes targeted treatment of cancer inaccurate for many individuals. Identifying actionable hyperactive biological pathways in individual cancers may improve this situation.To achieve this we applied a novel targeted RNA next generation sequencing (t/RNA-NGS) technique to surgically obtained glioma tissues. The test combines mutation detection with analysis of biological pathway activities that are involved in tumour behavior in many cancer types (e.g. tyrosine kinase signaling, angiogenesis signaling, immune response, metabolism), via quantitative measurement of transcript levels and splice variants of hundreds of genes. We here present proof of concept that the technique, which uses molecular inversion probes, generates a histology-independent molecular diagnosis and identifies classifiers that are strongly associated with conventional histopathology diagnoses and even with patient prognosis. The test not only confirmed known glioma-associated molecular aberrations but also identified aberrant expression levels of actionable genes and mutations that have so far been considered not to be associated with glioma, opening up the possibility of drug repurposing for individual patients. Its cost-effectiveness makes t/RNA-NGS to an attractive instrument to aid oncologists in therapy decision making.