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Score chart with predicted probability (%) to remain on WW at 12 months This model was based on the number of IMDC Risk factors (0, 1, 2), the number or involved organ sites (0 - 4) and the geometric mean [¹⁸F]FDG SUVmax as a continuous variable. The underlying formula is 100*(exp(-0.531)^exp(0.198*[IMDC score] + 0.039*[No of affected organ sites] + 0.170*[geometric mean [¹⁸F]FDG SUVmax] - 1.09))

Lasso model

Purpose:Watchful waiting (WW) can be considered for patients with metastatic clear-cell renal cell carcinoma (mccRCC) with good or intermediate prognosis, especially those with 18F]FDG PET/CT and [89Zr]Zr-DFO-girentuximab PET/CT for WW duration in patients with mccRCC.Experimental Design:Between February 2015 and March 2018, 48 patients were enrolled, including 40 evaluable patients with good (n = 14) and intermediate (n = 26) prognosis. Baseline contrast-enhanced CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab PET/CT were performed. Primary endpoint was the time to disease progression warranting systemic treatment. Maximum standardized uptake values (SUVmax) were measured using lesions on CT images coregistered to PET/CT. High and low uptake groups were defined on the basis of median geometric mean SUVmax of RECIST-measurable lesions across patients.Results:The median WW time was 16.1 months [95% confidence interval (CI): 9.0–31.7]. The median WW period was shorter in patients with high [18F]FDG tumor uptake than those with low uptake (9.0 vs. 36.2 months; HR, 5.6; 95% CI: 2.4–14.7; P < 0.001). Patients with high [89Zr]Zr-DFO-girentuximab tumor uptake had a median WW period of 9.3 versus 21.3 months with low uptake (HR, 1.7; 95% CI: 0.9–3.3; P = 0.13). Patients with “W&W criteria” had a longer median WW period of 21.3 compared with patients without: 9.3 months (HR, 1.9; 95% CI: 0.9–3.9; Pone-sided = 0.034). Adding [18F]FDG uptake to the “W&W criteria” improved the prediction of WW duration (P < 0.001); whereas [89Zr]Zr-DFO-girentuximab did not (P = 0.53).Conclusions:In patients with good- or intermediate-risk mccRCC, low [18F]FDG uptake is associated with prolonged WW. This study shows the predictive value of the “W&W criteria” for WW duration and shows the potential of [18F]FDG-PET/CT to further improve this.

Images from a kidney lamella after perfusion made with the clinical laparoscopic fluorescence camera showing normal kidney parenchyma (A): visible light image (B): corresponding fluorescence image.

Video made with the laparoscopic fluorescence camera during experiment #1.

Supplementary Materials- figure legends

Purpose: Antibodies labeled with both a near-infrared fluorescent dye and a radionuclide can be used for tumor-targeted intraoperative dual-modality imaging. Girentuximab is a chimeric monoclonal antibody against carbonic anhydrase IX (CAIX), an antigen expressed in 95% of clear cell renal cell carcinoma (ccRCC). This study aimed to assess the feasibility of targeted dual-modality imaging with 111In-girentuximab-IRDye800CW using ex vivo perfusion of human tumorous kidneys.Experimental Design: Seven radical nephrectomy specimens from patients with ccRCC were perfused during 11 to 15 hours with dual-labeled girentuximab and subsequently rinsed during 2.5 to 4 hours with Ringer's Lactate solution. Then, dual-modality imaging was performed on a 5- to 10-mm-thick lamella of the kidney. Fluorescence imaging was performed with a clinical fluorescence camera set-up as applied during image-guided surgery. The distribution of Indium-111 in the slice of tumor tissue was visualized by autoradiography. In two perfusions, an additional dual-labeled control antibody was added to demonstrate specific accumulation of dual-labeled girentuximab in CAIX-expressing tumor tissue.Results: Both radionuclide and fluorescence imaging clearly visualized uptake in tumor tissue and tumor-to-normal tissue borders, as confirmed (immuno)histochemically and by gamma counting. Maximum uptake of girentuximab in tumor tissue was 0.33% of the injected dose per gram (mean, 0.12 %ID/g; range, 0.01–0.33 %ID/g), whereas maximum uptake in the normal kidney tissue was 0.04 %ID/g (mean, 0.02 %ID/g; range, 0.00–0.04 %ID/g).Conclusions: Dual-labeled girentuximab accumulated specifically in ccRCC tissue, indicating the feasibility of dual-modality imaging to detect ccRCC. A clinical study to evaluate intraoperative dual-modality imaging in patients with ccRCC has been initiated. Clin Cancer Res; 22(18); 4634–42. ©2016 AACR.

Supplementary Figures S1-S3 from Cancer Patients Treated with Sunitinib or Sorafenib Have Sufficient Antibody and Cellular Immune Responses to Warrant Influenza Vaccination

Purpose: The tyrosine kinase inhibitors sorafenib and sunitinib have efficacy in several types of cancer. Recent studies indicate that these agents affect the immune system. The way it affects the immune response to influenza vaccination is unknown. The aim of this study was to elucidate the specific immune response to seasonal flu vaccination in cancer patients treated with sunitinib or sorafenib.Patients and Methods: Sunitinib- or sorafenib-treated cancer patients were vaccinated against seasonal influenza with an inactivated vaccine. Healthy controls and patients with metastatic renal cell cancer (mRCC) without systemic treatment (nontreated mRCC controls) were included for comparison. Antibody responses were measured at baseline, day 8, and day 22 by a standard hemagglutination inhibition assay and cellular T-cell responses at baseline and day 8 by proliferation assay and secretion of cytokines.Results: Forty subjects were enrolled: 16 patients treated with sunitinib, 6 patients with sorafenib, 7 nontreated mRCC controls, and 11 healthy controls. All patients treated with sunitinib and sorafenib developed seroprotection rates comparable with controls. Functional T-cell reactivity was observed in all groups, except for patients treated with sorafenib who showed a decreased proliferation rate and IFN-γ/IL-2 production and increased IL-10 compared with healthy controls.Conclusion: We conclude that influenza vaccination should be recommended to cancer patients treated with sunitinib or sorafenib. Clin Cancer Res; 17(13); 4541–9. ©2011 AACR.

Purpose: Watchful waiting (WW) can be considered for patients with metastatic clear-cell renal cell carcinoma (mccRCC) with good or intermediate prognosis, especially those with Experimental Design: Between February 2015 and March 2018, 48 patients were enrolled, including 40 evaluable patients with good (n = 14) and intermediate (n = 26) prognosis. Baseline contrast-enhanced CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab PET/CT were performed. Primary endpoint was the time to disease progression warranting systemic treatment. Maximum standardized uptake values (SUVmax) were measured using lesions on CT images coregistered to PET/CT. High and low uptake groups were defined on the basis of median geometric mean SUVmax of RECIST-measurable lesions across patients. Results: The median WW time was 16.1 months [95% confidence interval (CI): 9.0–31.7]. The median WW period was shorter in patients with high [18F]FDG tumor uptake than those with low uptake (9.0 vs. 36.2 months; HR, 5.6; 95% CI: 2.4–14.7; P < 0.001). Patients with high [89Zr]Zr-DFO-girentuximab tumor uptake had a median WW period of 9.3 versus 21.3 months with low uptake (HR, 1.7; 95% CI: 0.9–3.3; P = 0.13). Patients with “W&W criteria” had a longer median WW period of 21.3 compared with patients without: 9.3 months (HR, 1.9; 95% CI: 0.9–3.9; Pone-sided = 0.034). Adding [18F]FDG uptake to the “W&W criteria” improved the prediction of WW duration (P < 0.001); whereas [89Zr]Zr-DFO-girentuximab did not (P = 0.53). Conclusions: In patients with good- or intermediate-risk mccRCC, low [18F]FDG uptake is associated with prolonged WW. This study shows the predictive value of the “W&W criteria” for WW duration and shows the potential of [18F]FDG-PET/CT to further improve this.

Contains fulltext : 251789.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To analyse if exposure to sunitinib in the Immediate Surgery or Surgery After Sunitinib Malate in Treating Patients With Metastatic Kidney Cancer (SURTIME) trial, which investigated opposite sequences of cytoreductive nephrectomy (CN) and systemic therapy, is associated with the overall survival (OS) benefit observed in the deferred CN arm. PATIENTS AND METHODS: A post hoc analysis of SURTIME trial data. Variables analysed included number of patients receiving sunitinib, time from randomisation to start sunitinib, overall response rate by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, and duration of drug exposure and dose in the intention-to-treat population of the immediate and deferred arm. Descriptive methods and 95% confidence-intervals (CI) were used. RESULTS: In the deferred arm, 97.7% (95% CI 89.3-99.6%; n = 48) received sunitinib vs 80% (95% CI 66.9-88.7%, n = 40) in the immediate arm. Following immediate CN, 19.6% progressed 4 weeks after CN and the median time to start sunitinib was 39.5 vs 4.5 days in the deferred arm. At week 16, 46.0% had progressed at metastatic sites in the immediate CN arm vs 32.7% in the deferred arm. Sunitinib dose reductions, escalations and interruptions were not statistically significantly different between arms. Among patients who received sunitinib in the immediate or deferred arm the median total sunitinib treatment duration was 172.5 vs 248 days. Reduction of target lesions was more profound in the deferred arm. CONCLUSIONS: In comparison to the deferred CN approach, immediate CN impairs administration, onset, and duration of sunitinib. Starting with systemic therapy leads to early and more profound disease control and identification of progression prior to planned CN, which may have contributed to the observed OS benefit.

Item does not contain fulltext PURPOSE OF REVIEW: Conventional imaging is unable to differentiate clear cell renal cell carcinoma (ccRCC) from other more indolent and benign renal tumors. Positron emission tomography/computed tomography (PET/CT) using radiolabeled antibodies may aid in detecting both localized and metastatic ccRCC. The purpose of this review is to summarize recent literature regarding the use of radiolabeled antibodies for imaging of ccRCC. RECENT FINDINGS: Two recent studies evaluated the use of radiolabeled anticarbonic anhydrase IX antibody girentuximab for the imaging of ccRCC. PET/CT with 89zirconium-labeled girentuximab (89Zr-girentuximab PET/CT) was used to guide clinical decision making in 16 patients with localized disease. It had a high specificity for detecting ccRCC with 6/6 resected lesions with uptake proven to be ccRCC, all lesion without uptake showed to be indolent during follow-up. Clinical management was changed in 36% (5/14) of patients with the metastatic disease based on outcomes of the scan. Furthermore, in 42 patients 89Zr-girentuximab PET/CT combined with CT outperformed CT alone or combined with 18F fludeoxyglucose PET for detection of metastasis. SUMMARY: 89Zr-girentuximab PET/CT has the ability to diagnose ccRCC in localized disease. In metastatic disease, it enables the differentiation of ccRCC from non-ccRCC cancers and the evaluation of disease extent. 89Zr-girentuximab PET/CT diagnostic accuracy is currently evaluated in a multicenter phase III trial.

Purpose In this phase I study, we evaluated the safety, biodistribution and dosimetry of [89Zr]Zr-DFO-girentuximab (89Zr-girentuximab) PET/CT imaging in patients with suspicion of clear cell renal cell carcinoma (ccRCC). Methods Ten eligible patients received an intravenous administration of 37 MBq (± 10%) of 89Zr-girentuximab at mass doses of 5 mg or 10 mg. Safety was evaluated according to the NCI CTCAE (version 4.03). Biodistribution and normal organ dosimetry was performed based on PET/CT images acquired at 0.5, 4, 24, 72 and 168 h post-administration. Additionally, tumour dosimetry was performed in patients with confirmed ccRCC and visible tumour uptake on PET/CT imaging. Results 89Zr-girentuximab was administered in ten patients as per protocol. No treatment-related adverse events ≥ grade 3 were reported. 89Zr-girentuximab imaging allowed successful differentiation between ccRCC and non-ccRCC lesions in all patients, as confirmed with histological data. Dosimetry analysis using OLINDA/EXM 2.1 showed that the organs receiving the highest doses (mean ± SD) were the liver (1.86 ± 0.40 mGy/MBq), the kidneys (1.50 ± 0.22 mGy/MBq) and the heart wall (1.45 ± 0.19 mGy/MBq), with a mean whole body effective dose of 0.57 ± 0.08 mSv/MBq. Tumour dosimetry was performed in the 6 patients with histologically confirmed ccRCC resulting in a median tumour-absorbed dose of 4.03 mGy/MBq (range 1.90–11.6 mGy/MBq). Conclusions This study demonstrates that 89Zr-girentuximab is safe and well tolerated for the administered activities and mass doses and allows quantitative assessment of 89Zr-girentuximab PET/CT imaging in patients with suspicion of ccRCC. Trial registration NCT03556046—14th of June, 2018

Background Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of “unnecessary” prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naïve men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy. Methods This prospective multicenter diagnostic study included 599 biopsy-naïve patients with prostate-specific antigen level ≥3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) ≥ 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of ≥−2.8. Decision curve analysis (DCA) was performed to assess clinical utility. Results Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%. Conclusions SelectMDx test as a risk stratification tool for biopsy-naïve men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment option for major depressive disorder, so understanding whether its clinical effect relates to structural brain changes is vital for current and future antidepressant research. OBJECTIVE: To determine whether clinical response to ECT is related to structural volumetric changes in the brain as measured by structural magnetic resonance imaging (MRI) and, if so, which regions are related to this clinical effect. We also determine whether a similar model can be used to identify regions associated with electrode placement (unilateral versus bilateral ECT). METHODS: Longitudinal MRI and clinical data (Hamilton Depression Rating Scale) was collected from 10 sites as part of the Global ECT-MRI research collaboration (GEMRIC). From 192 subjects, relative changes in 80 (sub)cortical areas were used as potential features for classifying treatment response. We used recursive feature elimination to extract relevant features, which were subsequently used to train a linear classifier. As a validation, the same was done for electrode placement. We report accuracy as well as the structural coefficients of regions included in the discriminative spatial patterns obtained. RESULTS: A pattern of structural changes in cortical midline, striatal and lateral prefrontal areas discriminates responders from non-responders (75% accuracy, p

Contains fulltext : 244184.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Body composition has been associated with disease outcome in several cancer types. Results for localized and metastatic renal cell cancer (RCC) are limited and inconsistent. Our aim was to examine the association between body composition and survival in RCC. METHODS: We conducted a population-based historical cohort study including patients diagnosed with RCC from 2008 to 2012. Diagnostic Computed Tomography images at the third lumbar vertebra (L3) were assessed for skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI) and subcutaneous adipose tissue index (SATI). Clinical data was retrieved from medical records. Multivariable Cox regressions with restricted cubic splines were used to determine hazard ratios (HRs) and 95% confidence intervals (95%CIs) for 10-unit increases in body composition features with overall survival (OS) and recurrence-free survival (RFS). RESULTS: We included 719 stage I-III (of whom 254 (35.3%) died and 148 (21.9%) experienced recurrence) and 320 stage IV RCC patients (of whom 298 (93.1%) died). Median follow-up was 6.35 years (interquartile range; 1.41-8.23). For stage I-III, higher SMD was associated with better OS (men: HR 0.86; 95% CI 0.68-1.08; women: HR 0.69; 95% CI 0.50-0.95). Lower compared to median VATI was associated with worse OS for both men (HR 1.38; 95%CI 1.05-1.83 for VATI = 25) and women (HR 1.67; 95%CI 1.01-2.78 for VATI = 20). For stage IV, higher SMD and higher VATI were associated with better OS among men (HR 0.74; 95% CI 0.59-0.94 and HR 0.93; 95% CI 0.88-0.99, respectively). Results for women were similar but non-significant. No statistically significant associations were found for SMI or SATI. CONCLUSION: Higher SMD and higher VATI were marginally associated with better survival in RCC patients and might be useful for better prognostication. However, the added value to current prognostic scores needs to be investigated.

Background: Renal cell carcinoma (RCC) thrombus invasion in the inferior vena cava (IVC) wall needs adequate resection to improve survival. Surgical planning to avoid positive vascular surgical margins and recurrent disease can be facilitated by imaging capable of diagnosing this invasion and the extent of the thrombus. Objective: To evaluate the diagnostic performance of multiparametric MR imaging (mpMRI) for detecting inferior vena cava (IVC) wall invasion and extent of renal cell carcinoma (RCC) thrombus. Methods: In this prospective study, twenty consecutive patients underwent mpMRI before open radical nephrectomy with IVC thrombectomy was performed in a single high-volume institution by one urologist (PM) blinded for mpMRI findings. Primary endpoint was mpMRI negative- and positive predictive value (NPV/PPV) for IVC wall invasion as encountered during surgery. IVC wall invasion was assessed on mpMRI by a radiologist prior to the surgery based on qualitative imaging parameters. Also, NPV and PPV were calculated with incremental use of quantitative parameters. Therefore, the association between IVC wall invasion and the maximum IVC and renal vein orifice diameter, and the cranial extent of the thrombus was evaluated by logistic regression. After ROC analysis an optimal cut-off point was selected for significantly associated quantitative parameters. NPV and PPV were calculated using this optimal cut-off point. Results: mpMRI NPV and PPV for IVC wall invasion based on qualitative parameters was 82% and 100%, respectively. An increase in IVC diameter was significantly associated with IVC wall invasion (p

SamenvattingWat zouden we graag willen dat alles terug bij normaal was. Niets is minder waar. Toch hebben we weer een prachtige verzameling abstracts binnengekregen. De inhoud spreekt voor zich. Er wordt nog steeds veel en gevarieerd onderzoek gedaan. De variatie qua onderwerp duidt op de onmiskenbare breedheid van ons vakgebied.

BackgroundElectroconvulsive therapy (ECT) is the most effective intervention for patients with treatment resistant depression. A clinical decision support tool could guide patient selection to improve the overall response rate and avoid ineffective treatments with adverse effects. Initial small-scale, mono-center studies indicate that both structural magnetic resonance imaging (sMRI) and functional MRI (fMRI) biomarkers may predict ECT outcome, but it is not known whether those results can generalize to data from other centers.ObjectiveTo develop and validate neuroimaging biomarkers for ECT outcome in a multi-center setting.MethodsMultimodal data (i.e., clinical, sMRI and resting-state fMRI) was collected from seven centers of the Global ECT-MRI Research Collaboration (GEMRIC). We used data from 189 depressed patients to evaluated which data modalities or combinations thereof could provide the best predictions for treatment response (≥50% symptom reduction) or remission (HAM-D score ≤7) using a support vector machine classifier.ResultsRemission classification using a combination of gray matter volume and functional connectivity led to good performing models with average 0.82-0.83 area under the curve (AUC) when trained and tested on samples coming from the three largest centers, and remained acceptable when validated using leave-one-site-out cross-validation (0.70-0.73 AUC).ConclusionsThese results show that multimodal neuroimaging data is able to provide good prediction of remission with ECT for individual patients across different treatment centers, despite significant variability in clinical characteristics across centers. This suggests that these biomarkers are robust, indicating that future development of a clinical decision support tool applying these biomarkers may be feasible.

Purpose Detection of residual or recurrent vital renal tumor on follow-up (FU) cross-sectional imaging after ablative therapy is challenging. The specific and high expression levels of carbonic anhydrase IX (CAIX) in clear cell renal cell carcinoma (ccRCC) makes it a suitable target for imaging using radiolabeled anti-CAIX antibody girentuximab. The objective of this study was to evaluate the feasibility of targeted FU imaging 1 month after cryoablation of ccRCC using single photon emission computed tomography (SPECT) after 111In-labeled girentuximab administration. Methods In this prospective study 16 patients underwent 111In-girentuximab-SPECT before MR-guided renal cryoablation between February 2015 and September 2018. In case of tumor targeting 111In-girentuximab-SPECT was repeated 1 month following MR-guided cryoablation. Presence of residual or recurrent vital tumor was assessed on contrast-enhanced cross-sectional imaging during further FU. The standard FU imaging protocol consisted of MRI/CT scans at 1, 3, 6, 12, and 18 months and annually thereafter. Results A total of 10 (63%) patients showed positive tumor targeting on 111In-girentuximab-SPECT before cryoablation and 9 ( 56%) were eligible to undergo FU SPECT. Of the 9 111In-girentuximab-SPECT FU scans, 8 (89%) were considered negative. One (11%) scan showed uptake suggestive for residual vital tumor. Six months after treatment, FU CT showed contrast enhancement suggestive for residual/recurrent disease in the ablated zone at the site of the 111In-girentuximab uptake after treatment. During a mean FU of 21 months (range 1–33) no other cases with residual/recurrent disease were detected. Conclusion FU imaging with 111In-girentuximab-SPECT is feasible after ccRCC cryoablation and may contribute to early detection of residual or recurrent disease.

Samenvatting Biochemisch recidiverende prostaatkanker na curatieve radiotherapie is gedefinieerd als een PSA-stijging van ≥ 2 ng/ml boven de PSA nadir (de Phoenix-criteria, 2005). Met de introductie van prostaatspecifiek membraan antigeen (PSMA) PET/CT is de mogelijkheid tot lokalisatie van recidieven van prostaatkanker sterk toegenomen. In deze studie analyseren we de uitkomsten van PSMA PET/CT ter detectie van recidiverende prostaatkanker bij patiënten met een stijgend PSA na radiotherapie, die nog niet voldoen aan de Phoenixcriteria (i.e. een PSA-stijging < 2,0 ng/ml).

The European Organisation for Research and Treatment of Cancer SURTIME trial explored timing of sunitinib, a tyrosine kinase inhibitor (TKI), and cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma. Previous retrospective studies suggest increased surgeryrelated adverse events (AEs) after presurgical TKI. We report surgical safety from a randomised comparison of CN before or after sunitinib. In-hospital mortality, 30-d readmission rate, and intraoperative and 30-d postoperative AEs according to Common Terminology Criteria for Adverse Events version 4 and Clavien-Dindo (CD) were analysed. Patients were randomised 1:1 to immediate CN followed by sunitinib versus sunitinib followed by deferred CN 24 h after the last dose of sunitinib. None of the tumours in the deferred arm became unresectable, and only two patients had a sunitinib-related delay of CN of >2 wk. AEs related to surgery (all grades) in the immediate and deferred arms occurred in 52% and 53% after CN, respectively, although the number of intraoperative surgery-related AEs was higher in the immediate arm. Postoperative AEs (CD >= 3), 30-d readmission, and in-hospital mortality rates were 6.5%, 13%, and 4.3% in the immediate arm and 2.5%, 7.5%, and 2.5% in the deferred arm, respectively. There were no differences in surgery time, blood loss, and hospital stay.Patient summary: Patients with metastatic kidney cancer do not have more surgical complications irrespective of whether they are treated with systemic therapy before or after surgery. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The MAGNOLIA study, investigating the concept of perioperative immunotherapy in muscle- invasive bladder cancer, was prematurely terminated. The lessons learned that should be considered before initiating and conducting future clinical trials in this field are highlighted.

Importance: In clinical practice, patients with primary metastatic renal cell carcinoma (mRCC) have been offered cytoreductive nephrectomy (CN) followed by targeted therapy, but the optimal sequence of surgery and systemic therapy is unknown. Objective: To examine whether a period of sunitinib therapy before CN improves outcome compared with immediate CN followed by sunitinib. Design, Setting, and Participants: This randomized clinical trial began as a phase 3 trial on July 14, 2010, and continued until March 24, 2016, with a median follow-up of 3.3 years and a clinical cutoff date for this report of May 5, 2017. Patients with mRCC of clear cell subtype, resectable primary tumor, and 3 or fewer surgical risk factors were studied. Interventions: Immediate CN followed by sunitinib therapy vs treatment with 3 cycles of sunitinib followed by CN in the absence of progression followed by sunitinib therapy. Main Outcomes and Measures: Progression-free survival was the primary end point, which needed a sample size of 458 patients. Because of poor accrual, the independent data monitoring committee endorsed reporting the intention-to-treat 28-week progression-free rate (PFR) instead. Overall survival (OS), adverse events, and postoperative progression were secondary end points. Results: The study closed after 5.7 years with 99 patients (80 men and 19 women; mean [SD] age, 60 [8.5] years). The 28-week PFR was 42% in the immediate CN arm (n = 50) and 43% in the deferred CN arm (n = 49) (P =.61). The intention-to-treat OS hazard ratio of deferred vs immediate CN was 0.57 (95% CI, 0.34-0.95; P =.03), with a median OS of 32.4 months (95% CI, 14.5-65.3 months) in the deferred CN arm and 15.0 months (95% CI, 9.3-29.5 months) in the immediate CN arm. In the deferred CN arm, 48 of 49 patients (98%; 95% CI, 89%-100%) received sunitinib vs 40 of 50 (80%; 95% CI, 67%-89%) in the immediate arm. Systemic progression before planned CN in the deferred CN arm resulted in a per-protocol recommendation against nephrectomy in 14 patients (29%; 95% CI, 18%-43%). Conclusions and Relevance: Deferred CN did not improve the 28-week PFR. With the deferred approach, more patients received sunitinib and OS results were higher. Pretreatment with sunitinib may identify patients with inherent resistance to systemic therapy before planned CN. This evidence complements recent data from randomized clinical trials to inform treatment decisions in patients with primary clear cell mRCC requiring sunitinib. Trial Registration: ClinicalTrials.gov identifier: NCT01099423., SCOPUS: cp.j, info:eu-repo/semantics/published

Het doel van deze studie is de veiligheid en toepasbaarheid van carbonzuuranhydrase IX (CAIX)-targeted dual-modality imaging bij een heldercellig niercelcarcinoom (ccRCC) te onderzoeken. Zeven dagen voor de partiele of totale nefrectomie werden patienten geinjecteerd met 100MBq 111In-girentuximab-IRDye800CW (5–50 mg). Op dag vier werd een SPECT/CT-scan gemaakt. Op dag zeven was de operatie waarbij een gamma probe en een fluorescentiecamera gebruikt werden voor intraoperatieve tumordetectie. 15 patienten werden geincludeerd: 12 met CAIX-positieve en 3 met CAIX-negatieve tumoren. Studiegerelateerde ernstige bijwerkingen werden niet gezien. Alle ccRCC’s waren preoperatief zichtbaar op de SPECT/CT-scan en konden intraoperatief gelokaliseerd worden met de gamma probe (tumor: normale nierratio 2,5 ± 0,8), terwijl de gemiddelde tumor: normale nierratio 1,0 ± 0,1 was in CAIX-negatieve tumoren. Alle ccRCC’s waren hyperfluorescent en fluorescentie-imaging toonde een positief snijvlak. Conclusie: Tumor-targeted dual-modality imaging met 111In-girentuximab-IRDye800CW is veilig en kan worden gebruikt voor de intraoperatieve detectie van ccRCC.

Item does not contain fulltext BACKGROUND: Electroconvulsive therapy (ECT) is a highly effective treatment for depression but how it achieves its clinical effects remains unclear. METHODS: We set out to study the brain's response to ECT from a large-scale brain-network perspective. Using a voxelwise analysis, we looked at resting-state functional connectivity before and after a course of ECT at the whole-brain and the between- and within-network levels in 17 patients with a depressive episode. Using a group-independent component analysis approach, we focused on four networks known to be affected in depression: the salience network (SN), the default mode network (DMN), the cognitive executive network (CEN), and a subcortical network (SCN). Our clinical measures included mood, cognition, and psychomotor symptoms. RESULTS: We found ECT to have increased the connectivity of the left CEN with the left angular gyrus and left middle frontal gyrus as well as its within-network connectivity. Both the right CEN and the SCN showed increased connectivity with the precuneus and the anterior DMN with the left amygdala. Finally, improvement of psychomotor retardation was positively correlated with an increase of within-posterior DMN connectivity. LIMITATIONS: The limitations of our study include its small sample size and the lack of a control dataset to confirm our findings. CONCLUSION: Our voxelwise data demonstrate that ECT induces a significant increase of connectivity across the whole brain and at the within-network level. Furthermore, we provide the first evidence on the association between an increase of within-posterior DMN connectivity and an improvement of psychomotor retardation, a core symptom of depression.

Major depressive disorder (MDD) is amongst the most prevalent of psychiatric disorders. Unfortunately, a third of patients will not respond to conventional treatments and suffer from treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) has been proven effective in treating TRD. The research suggests that rTMS acts via neuroplastic effects on the brain, which can be measured by changes in hippocampal and amygdala volume as well as cortical thickness. This sham-controlled study investigates longitudinal effects of rTMS on the volumes of the hippocampus and amygdala and cortical thickness in patients with chronic TRD. 31 patients received 20 sessions of high-frequency rTMS (N = 15) or sham treatment (N = 16) over the left dorsolateral prefrontal cortex during 4 consecutive weeks. Using structural magnetic resonance imaging, we investigated longitudinal treatment effects on hippocampus and amygdala volume as well as thickness of the paralimbic cortex. We found no clinical differences between the active and sham rTMS group. Longitudinal changes in hippocampal and amygdala volume did not differ significantly, although males showed a significant decrease in left amygdala volume, irrespective of treatment group. Changes in cortical thickness of the paralimbic cortex differed significantly between the active and sham groups. Most notably, the increase in cortical thickness of the isthmus of the left cingulate gyrus was greater in the active as compared to the sham rTMS group. Our data suggest that rTMS can induce neuroplastic changes, particularly in cortical thickness, independent of treatment response. We also found longitudinal changes in amygdala volume in males. For clinical effects to follow these neuroplastic effects, more intensive rTMS treatment might be needed in chronically depressed patients. Trial registration number: ISRCTN 15535800, registered on 29-06-2017. Electronic supplementary material The online version of this article (10.1007/s00406-020-01135-w) contains supplementary material, which is available to authorized users.

PURPOSE To assess the ability to discriminate oncocytoma from RCC based on a model using whole tumor ADC histogram parameters with additional use of tumor volume and patient characteristics. METHOD In this prospective study, 39 patients (mean age 65 years, range 28-79; 9/39 (23%) female) with 39 renal tumors (32/39 (82%) RCC and 7/39 (18%) oncocytoma) underwent multiparametric MRI between November 2014 and June 2018. Two regions of interest (ROIs) were drawn to cover both the entire tumor volume and a part of healthy renal cortex. ROI ADC maps were calculated using a mono-exponential model and ADC histogram distribution parameters were calculated. A logistic regression model was created using ADC histogram parameters, radiographic and patient characteristics that were significantly different between oncocytoma and RCC. A ROC curve of the model was constructed and the AUC, sensitivity and specificity were calculated. Furthermore, differences in intra-patient ADC histogram parameters between renal tumor and healthy cortex were calculated. A separate ROC curve was constructed to differentiate oncocytoma from RCC using statistically significant intra-patient parameter differences. RESULTS ADC standard deviation (p = 0.008), entropy (p = 0.010), tumor volume (p = 0.012), and patient sex (p = 0.018) were significantly different between RCC and oncocytoma. The regression model of these parameters combined had an ROC-AUC of 0.91 with a sensitivity of 86% and specificity of 84%. Intra-patient difference in ADC 25th percentile (p

Item does not contain fulltext BACKGROUND: PSMA-PET is a novel imaging modality for the staging of prostate cancer (PCa). While there are several PSMA ligands available, F-18-PSMA-1007 is particularly of interest as it is not renally excreted and therefore does not impair the imaging of the pelvic area. Hence, this study aimed to investigate the F-18-PSMA-1007-PET for the primary staging of PCa and compared it to multi-parametric (mp) MRI and histopathology. METHODS: A retrospective study was performed of men with intermediate and high-risk PCa patients that underwent a F-18-PSMA-1007-PET after mpMRI with subsequent MR-guided target biopsy (MRGB). Suspicious mpMRI lesions and F-18-PSMA-1007-PET were simultaneously reviewed on both a per patient and per-lesion basis. Results were subsequently evaluated with histopathological outcome of MRGB, and if performed, the radical prostatectomy specimen. RESULTS: A total of 66 suspicious mpMRI lesions were identified in 53 patients and underwent MRGB. Two lesions had a maximum standardized uptake value (SUV(max)) less than the mean SUV(max) of healthy prostate tissue and were considered as non-PSMA-expressing. All PSMA avid tumors had higher SUV(max) than the mean SUV(mean) of the bladder/urine, therefore all lesions were clearly distinguishable in the pelvic area. Twenty-three patients received a radical prostatectomy of which the histopathology specimens were evaluated. F-18-PSMA-1007-PET/CT correctly staged seminal vesicle invasion (i.e. pT3b) more often than mpMRI (90 vs. 76%), whereas mpMRI more accurately detected extracapsular extension (i.e. pT3a) compared to F-18-PSMA-1007-PET (90% vs 57%). CONCLUSIONS: The present study of a selected cohort suggest that dual imaging with mpMRI and F-18-PSMA-1007-PET may improve staging of primary PCa. F-18-PSMA-1007-PET/CT had low renal clearance, which could assist the evaluation of tumors in proximity of the bladder.

Carbonic anhydrase IX (CAIX) is a transmembranous enzyme that is present in multiple carcinomas, including clear cell renal cell carcinoma (ccRCC). CAIX is a validated cell marker for hypoxia, an important asset in the prediction of radiotherapeutic efficacy. CAIX expression in ccRCC is high and homogenous, the consequence of mutations in the von Hippel Lindau gene, leading to a pseudohypoxic phenotype. CAIX is recognized, amongst others, by the monoclonal antibody G250. The high expression of CAIX in the most common malignant renal cancer in combination with very limited expression in normal tissue endorses CAIX as a promising candidate for multiple antibody-based applications in this disease. This chapter explores potential clinical applications, including the guidance of clinical decision making in case of diagnostic dilemmas concerning ccRCC suspicion, the use of real-time monitoring of surgical margins during renal surgery, the development of novel therapeutic options in patients with advanced ccRCC, and the use of CAIX imaging in hypoxic tumors.

Contains fulltext : 233937.pdf (Publisher’s version ) (Closed access) BACKGROUND: Owing to the large variation in treatment response among patients with high-risk prostate cancer, it would be of value to use objective tools to monitor the status of bone metastases during clinical trials. Automated Bone Scan Index (aBSI) based on artificial intelligence has been proposed as an imaging biomarker for the quantification of skeletal metastases from bone scintigraphy. OBJECTIVE: To investigate how an increase in aBSI during treatment may predict clinical outcome in a randomised controlled clinical trial including patients with high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively selected all patients from the Zometa European Study (ZEUS)/SPCG11 study with image data of sufficient quality to allow for aBSI assessment at baseline and at 48-mo follow-up. Data on aBSI were obtained using EXINIbone(BSI) software, blinded for clinical data and randomisation of zoledronic acid treatment. Data on age, overall survival (OS), and prostate-specific antigen (PSA) at baseline and upon follow-up were available from the study database. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Association between clinical parameters and aBSI increase during treatment was evaluated using Cox proportional-hazards regression models, Kaplan-Meier estimates, and log-rank test. Discrimination between prognostic variables was assessed using the concordance index (C-index). RESULTS AND LIMITATIONS: In this cohort, 176 patients with bone metastases and a change in aBSI from baseline to follow-up of ≤0.3 had a significantly longer median survival time than patients with an aBSI change of >0.3 (p

Simple Summary In prostate cancer diagnosis and prognosis, clinicians often must take decisions on which prostate cancer-suspected patients should undergo biopsy and which prostate cancer-diagnosed patients should undergo treatment, to overcome overdiagnosis and overtreatment. Many biomarker-based tests have been developed and commercialized in order to guide decision-making processes of clinicians. Since a variety of biomarker-based tests are currently available, this review provides an overview of all commercially available tests for prostate cancer diagnosis and prognosis. For the diagnostic setting, the PHI, 4K, MiPS, SelectMDx, ExoDx, Proclarix, ConfirmMDx, PCA3 and PCMT are discussed, while for the prognostic setting, the Prolaris, OncotypeDx and Decipher test are discussed. Following, an overview is provided of the studies available comparing the performance of biomarker tests. Next, the use of biomarker tests complementary to the use of multiparametric magnetic resonance imaging in diagnosis of prostate cancer is discussed, which is an upcoming tool in prostate cancer diagnosis. Abstract In the diagnosis and prognosis of prostate cancer (PCa), the serum prostate-specific antigen test is widely used but is associated with low specificity. Therefore, blood-, urinary- and tissue-based biomarker tests have been developed, intended to be used in the diagnostic and prognostic setting of PCa. This review provides an overview of commercially available biomarker tests developed to be used in several clinical stages of PCa management. In the diagnostic setting, the following tests can help selecting the right patients for initial and/or repeat biopsy: PHI, 4K, MiPS, SelectMDx, ExoDx, Proclarix, ConfirmMDx, PCA3 and PCMT. In the prognostic setting, the Prolaris, OncotypeDx and Decipher test can help in risk-stratification of patients regarding treatment decisions. Following, an overview is provided of the studies available comparing the performance of biomarker tests. However, only a small number of recently published head-to-head comparison studies are available. In contrast, recent research has focused on the use of biomarker tests in relation to the (complementary) use of multiparametric magnetic resonance imaging in PCa diagnosis.

SamenvattingAlhier het abstractnummer van ons Tijdschrift. Niet zomaar een nummer: het zijn de abstracts die live gepresenteerd gaan worden tijdens het wetenschappelijk gedeelte van de voorjaarsvergadering van de NVU in Arnhem. Terug naar het normaal. Ondanks het feit dat de digitale voordrachten niet slecht gingen, is het natuurlijk veel beter om live reflectie te krijgen op je wetenschappelijk werk.

Item does not contain fulltext PURPOSE: To determine the value of two-dimensional (2D) contrast-enhanced ultrasound (CEUS) imaging and the additional value of contrast ultrasound dispersion imaging (CUDI) for the localization of clinically significant prostate cancer (csPCa). METHODS: In this multicentre study, subjects scheduled for a radical prostatectomy underwent 2D CEUS imaging preoperatively. CUDI maps were generated from the CEUS recordings. Both CEUS recordings and CUDI maps were scored on the likelihood of presenting csPCa (any Gleason ≥ 4 + 3 and Gleason 3 + 4 larger than 0.5 mL) by five observers and compared to radical prostatectomy histopathology. An automated three-dimensional (3D) fusion protocol was used to match imaging with histopathology. Receiver operator curve (ROC) analysis was performed per observer and imaging modality. RESULTS: 133 of 216 (62%) patients were included in the final analysis. Average area under the ROC for all five readers for CEUS, CUDI and the combination was 0.78, 0.79 and 0.78, respectively. This yields a sensitivity and specificity of 81 and 64% for CEUS, 83 and 56% for CUDI and 83 and 55% for the combination. Interobserver agreement for CEUS, CUDI and the combination showed kappa values of 0.20, 0.18 and 0.18 respectively. CONCLUSION: The sensitivity and specificity of 2D CEUS and CUDI for csPCa localization are moderate. Despite compressing CEUS in one image, CUDI showed a similar performance to 2D CEUS. With a sensitivity of 83% at cutoff point 3, it could become a useful imaging procedure, especially with 4D acquisition, improved quantification and combination with other US imaging techniques such as elastography.

5079 Background: In metastatic clear cell renal cell carcinoma (mccRCC), the number of International Metastatic Database Consortium (IMDC) risk factors plus metastatic sites may identify patients with rapid or slow disease progression in a period of watchful waiting (WW) (median WW of 8.4 vs 22.2 months; Rini et al. Lancet Oncol. 2016). We aimed to validate this and prospectively assess the added value of baseline PET with [18F]FDG and [89Zr]Zr-DFO-girentuximab to predict the WW-period in the multicenter IMaging PAtients for Cancer drug selecTion (IMPACT)-RCC cohort study. (NCT02228954). Methods: Between February 2015 and March 2018, 40 treatment-naïve mccRCC patients with a good (n=13) or intermediate prognosis (n=25) according to IMDC, were enrolled. Following baseline CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab-PET, CT scans (RECIST1.1) were acquired at 2, 4, 6, 9, 12 months and thereafter every 4 months. Primary endpoint was time to radiological and/or clinical disease progression, requiring systemic treatment. Patients were assigned to a favorable (max) were measured in PET-positive lesions measuring ≥10mm, or 15mm in lymph nodes. High and low-uptake groups were defined based on median geometric mean (gm) SUVmax across patients. A one-sided test was used to validate observations by Rini et al; other tests were two-sided. Results: The median WW-period was 9.3 months in the unfavorable WW-group (n=19) vs 20.4 months in the favorable WW-group (n=21) (HR 1.89 95%CI 0.94-3.89; p=0.037), confirming observations of Rini et al. Patients with high [18F]FDG uptake had a median WW-period of 8.5 months compared to 25.2 months in the low-uptake group (HR 4.08 95%CI 1.89-9.28; p=0.0002). Patients with high [89Zr]Zr-DFO-girentuximab uptake had a median WW-period of 10.7 versus 16.4 months in the low-uptake group (HR 1.37; 95%CI 0.69-2.76; p=0.37). [18F]FDG uptake groups improved a Cox-model for WW based on the prognostic groups of Rini et al (p=0.0015); [89Zr]Zr-DFO-girentuximab did not (p=0.98). Conclusions: The IMPACT-RCC study validated the observations by Rini et al. and shows that adding baseline [18F]FDG PET further improves the prediction of the duration of the WW-period in mccRCC patients. Clinical trial information: NCT02228954 .

Contains fulltext : 219107.pdf (Publisher’s version ) (Open Access) Background: Treatment options for major depressive disorder (MDD) in individuals who are depressed for at least 2 years and failed two or more different types of therapeutic intervention, remain scarce. Being less invasive than electroconvulsive therapy, repetitive transcranial magnetic stimulation (rTMS) might be an alternative treatment option. Research Question: Does high frequency rTMS applied over the left prefrontal cortex ameliorate depressive symptoms in patients with treatment resistant major depressive disorder and is the efficacy dependent on treatment resistance? Method: We performed a randomized controlled trial investigating the effect of twenty sessions of real or sham-rTMS, during 4 consecutive weeks. Efficacy was blindly rated with the Hamilton depression rating scale (HDRS-17) at baseline and 1 week after end of treatment, and the Dutch method for quantification of treatment resistance in Depression (DM-TRD) was assessed at baseline. Results: An interim analysis showed no differences in antidepressant response between real and sham rTMS and we therefore discontinued the RCT after 31 patients. The mean difference of the HDRS score between baseline and post-treatment was 3.7 (± 4.0; change 16%), indicating a small but significant improvement across time (F(1,30)=25.4;p

Contains fulltext : 215914.pdf (Publisher’s version ) (Closed access) Stressors induce physiological changes in the brain and periphery that support adaptive defensive responses. The consequences of psychological stress on cognitive functioning are often measured in laboratory settings using experimentally induced stress that leads to mainly negative subjective feelings. There is a need for verification of these studies using real-life stressors that may potentially induce both positive and negative subjective feelings. In an observational study, we investigated real-life stress induced by voluntary stage performance at a large-scale music festival, including 126 participants (60 female, age range = 16-57 years). Our primary measurements involved salivary cortisol, heart rate, blood pressure, and positive and negative affect. In addition, participants completed a 2-back working memory task and a speeded decision-making task. We found that stage performance significantly increased salivary cortisol - with a particularly low number of cortisol non-responders - and heart rate, even when controlling for potential confounding factors, such as sleep, movement, and alcohol use. Interestingly, stage performance significantly decreased negative affect while increasing positive affect. This positively experienced stressor ("eustressor") was related to impaired working memory performance: the stronger the increases in cortisol, the slower participants responded to targets. Decision-making, however, was not affected. In conclusion, we show how stressful experiences in real-life can lead to positive affect, but still have a similar negative impact on cognitive functioning. We suggest that future research should focus more on the consequences of real-life stressors, and the consequences of eustress, in order to extend our understanding of the concept of psychological stress. 11 p.

Kidney cancer is a heterogeneous disease encompassing 16 different Renal Cell tumor entities. Massive sequencing efforts have provided the opportunity to comprehensively molecularly characterize the three histological Renal Cell Carcinoma (RCC) entities that combined comprise 90–95% of RCC: clear cell RCC, papillary RCC and chromophobe RCC. Comprehensive analysis of genomic data has shown that even within histological homogeneous subtypes, genomic subtypes can be distinguished. Several molecular features are emerging as possible predictive biomarkers but the clinical utility of these candidate biomarkers still needs to be validated. Challenges are the high intratumor heterogeneity, lack of molecular signatures of metastatic RCC and lack of biomarkers for non-clear cell RCC. Nevertheless, molecular subclassification will have major ramifications in the future for the clinical management of RCC patients who were formally treated homogeneously. Indeed, personalized medicine, which is foreseen as the next step forward in cancer management, is likely to become possible for RCC based on detailed molecular knowledge.

Background: The validity of prediction models needs external validation to assess their value beyond the original development setting. Objective: To report the diagnostic accuracy of the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (RC)3 and RC4 in a contemporary Dutch clinical cohort. Design, setting, and participants: We retrospectively identified all men who underwent prostate biopsy (PBx) in the Jeroen Bosch Hospital, The Netherlands, between 2007 and 2016. Patients were included if they met ERSPC RC requirements of age (50–80 yr), prostate-specific antigen (PSA) (0.4–50 ng/ml), and prostate volume (10–150 ml). The probability of a positive biopsy for prostate cancer (PCa) and significant PCa (Gleason score ≥7 and/or higher than T2b) were calculated and compared with PBx pathology results. Outcome measurements and statistical analysis: Evaluation was performed by calibration, discrimination, and clinical usefulness using calibration plots, area under the receiver operating characteristic curves (AUCs), and decision curve analyses (DCAs), respectively. Results and limitations: A total of 2270 PBx sessions were eligible for final analysis. Discriminative ability of RC3 (AUC) was 0.78 and 0.90 for any PCa and significant PCa, respectively. For RC4 the calculated AUCs were 0.62 (any PCa) and 0.76 (significant PCa). The calibration plots of RC3 showed good results for both any PCa risk and significant PCa risk. In the repeat PBx group, RC4 tended to underestimate outcomes for PCa and showed moderate calibration for significant PCa. DCA showed an overall net benefit compared with PSA and digital rectal examination (DRE) alone. Limitations of this study are its retrospective single-institution design, retrospectively assessed DRE outcomes, no time restrictions between the first and repeat biopsy sessions, and no anterior sampling in the repeat PBx protocol. Conclusions: The ERSPC RCs performed well in a contemporary clinical setting. Most pronounced in the biopsy-naive group, both RCs should be favoured over a PSA plus DRE–based stratification in the decision whether or not to perform PBx. Patient summary: We looked at the ability of the existing European Randomized Study of Screening for Prostate Cancer risk calculator (RC), using different clinical data to predict the presence of prostate cancer in Dutch men. The RC performed well and should be favoured in the decision of whether or not to perform prostate biopsies over the conventional diagnostic pathway. The European Randomised Screening for Prostate Cancer risk calculators should be favoured over a prostate-specific antigen plus digital rectal examination–based stratification in the decision whether or not to perform prostate biopsy. An individualised approach for prostate cancer detection may reduce the adverse effects of our diagnostic approaches and/or treatments.

SamenvattingVoor u ligt weer het volgende nummer van Tijdschrift voor Urologie. Dit keer met de abstracts van de Najaarsvergadering van de NVU. We zijn er inmiddels aan gewend dat we elkaar minder vaak zien, dat de interactie nog steeds veelal digitaal is en dat er nog steeds wetenschap wordt bedreven. Interessant is het om te zien of de inhoud van de abstracts anders is geworden. De urologische praktijk wél. Hoe? Dat weten we nog niet in detail. Andere prioriteiten, andere volgorde?

Contains fulltext : 173185.pdf (Publisher’s version ) (Closed access) Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naive metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28-0.37; p

Contains fulltext : 174128.pdf (Publisher’s version ) (Closed access) In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302. Prostate-specific antigen (PSA) response was assessed. Median time to PSA progression was estimated using the Kaplan-Meier method. The PSA response rate (>/=50% PSA decline, unconfirmed) was 44% and 67%, respectively. The median time to PSA progression was 3.9 mo (range 2.6-not estimable) for subsequent abiraterone acetate plus prednisone and 2.8 mo (range 1.8-not estimable) for subsequent enzalutamide. The majority of patients (68%) received intervening chemotherapy before subsequent abiraterone acetate plus prednisone or enzalutamide. While acknowledging the limitations of post hoc analyses and high censoring (>75%) in both treatment groups, these results suggest that subsequent therapy with abiraterone acetate plus prednisone or enzalutamide for patients who progressed on abiraterone acetate is associated with limited clinical benefit. PATIENT SUMMARY: This analysis showed limited clinical benefit for subsequent abiraterone acetate plus prednisone or enzalutamide in patients with metastatic castration-resistant prostate cancer following initial treatment with abiraterone acetate plus prednisone. This analysis does not support prioritization of subsequent abiraterone acetate plus prednisone or enzalutamide following initial therapy with abiraterone acetate plus prednisone.

Functional connectivity between brain regions is modulated by cognitive states or experimental conditions. Such connectivity variations can be appreciated in covariance or correlation matrices obtained from fMRI data. A multivariate methodology that can capture fMRI connectivity maps in light of different experimental conditions would be of primary importance to learn about the specific roles of the different brain areas involved in the observed connectivity variations. Here we introduce Spatial Patterns for Discriminative Estimation (SP♠DE), a supervised dimensionality reduction model that provides a full multivariate characterization by achieving optimal discriminative linear spatial filters in terms of variance and provides interpretable spatial maps directly reflecting the brain areas involved in the accounted connectivity changes. We demonstrate the strength of SPADE using fMRI data from the Human connectome project to show that the model provides close to perfect discrimination between different fMRI tasks at low dimensionality. Additionally, the straightforward interpretability of the model is demonstrated by the obtained linear filters relating to anatomical areas well known to be involved in each considered fMRI task. Further, we also show that such an approach provides an alternative view to traditional task fMRI analyses by looking at changes in the covariance structure as a substitute to changes in the mean signal as the general linear model (GLM) analyses. We use 2-back and 0-back working memory task fMRI data from the Human connectome project to show that SPADE discovers connectivity changes in memory related areas during the 2-back periods, while attention network areas are involved during the 0-back task periods. We conclude that SPADE is a robust tool to investigate brain connectivity alterations across induced cognitive changes and has the potential to be used in pathological or pharmacological cohort studies.

To evaluate the feasibility of ex vivo 7T MRI to assess surgical margins (SMs) and pseudocapsule (PC) features after partial nephrectomy (PN). In this prospective, IRB-approved study, seven patients undergoing a PN for nine tumours between November 2014 and July 2015 were included for analysis after obtaining informed consent. MRI of the specimen was acquired using a 7T small bore scanner. The imaging protocol consisted of anatomical T1-, T2- and diffusion-weighted imaging. After formalin fixation, specimens were cut for pathology work-up in the same orientation as the MR images were obtained. The entire specimen was processed into H&E slides that were digitally scanned, annotated and correlated with radiological findings for negative SMs, PC presence, PC continuity and extra-PC-extension (EPCE). Sensitivity and specificity of MRI for assessment of these endpoints were calculated. The sensitivity and specificity for assessment of the SM were 100% and 75%, respectively. Two false-positive outcomes were reported, both in case of EPCE and a SM ≤0.5 mm. For the presence of a PC, sensitivity and specificity were 100% and 33%, respectively. Two false-positive scans with anatomical structures mimicking the presence of a PC occurred. If a PC was present, continuity and EPCE were assessed with a sensitivity and specificity of 75% and 100% and 67% and 100%, respectively. Ex vivo 7T MRI is a feasible tool for perioperative evaluation of SMs, and if present, PC features after PN. This may facilitate maximal sparing of renal parenchyma without compromising oncological outcomes. • Ex vivo MRI may contribute to improvement of negative surgical margins during partial nephrectomy. • Due to the assessment of surgical margins within a limited time span from obtaining the partial nephrectomy specimen, surgery for more complex tumours is possible with maximum sparing of healthy renal parenchyma without compromising oncological outcomes. • The intra operative assessment of pseudocapsule continuity along the resection margin enables maximal sparing of healthy renal parenchyma without delayed diagnosis of incomplete resection.

Clear cell renal cell carcinoma (ccRCC) comprises more than 80% of all renal cancers and when metastasized leads to a 5-year survival rate of only 10%. The high rate of therapy failure and resistance development calls for reliable methods that provide information on the actionable biological pathways and predict optimal treatment protocols for individual patients. We here applied targeted RNA sequencing (t/RNA-NGS) using single molecule Molecular Inversion Probes on tumor nephrectomy samples of five ccRCC patients, comparing tumor with healthy kidney tissues. Transcriptome profiling focused on expression of genes with involvement in ccRCC biology that can be targeted with clinically available drugs. Results confirm high expression of vascular endothelial growth factor-A (VEGF-A) in tumor tissue relative to healthy-appearing kidney, in line with the angiogenic nature of ccRCC. PDGFRα and KIT, targets of the multi-kinase inhibitor sunitinib which is one of the current choices of first-line drug in metastasized ccRCC patients, were expressed at relatively low levels in tumor tissues, whereas significantly increased in normal kidney. Of all measured druggable tyrosine kinases, MET, AXL, or EGFR were expressed at higher levels in tumors than in normal kidney tissues, although intertumor differences were observed. Using cancer cell lines we show that t/RNA-NGS gene expression profiles can be used to predict in vitro sensitivity to targeted drugs. In conclusion, t/RNA-NGS analysis may provide insights into the (druggable) molecular make-up of individual renal cancers, and may guide personalized therapy of renal cell cancers.