Intra/inter-observer reliability of cystoscopic sphincter evaluation in men undergoing sling surgery.

OBJECTIVES: To assess the intra/inter-observer reliability of cystoscopic sphincter evaluation (CSE) in men undergoing sling surgery for urinary incontinence and if possible to evaluate its correlation with the final clinical decision. PATIENTS AND METHODS: Two expert urologists prospectively filmed and recorded, incontinent patient's cystoscopies according to a standard scenario. Anonymised recordings where randomly offered to the same observer twice. The observers (medical students, urology residents and full urologist with 0-5, 5-10, >10 years of practice, respectively) were asked to assess and score the recordings without knowing any of the patients' characteristics. RESULTS: In total, 37 recordings were scored twice by the 26 observers. The intraclass correlation coefficient (ICC) for intra-observer reliability of the CSE was 0.54 (moderate), 0.58 (moderate) and 0.60 (substantial) for medical students, residents, and urologists, respectively. However, when stratifying observers according to their experience, the lowest agreement values were found between experts with >10 years of experience. The inter-observer reliability for the CSE ICCs ranged between 0.31and 0.53, with the lowest ICC value observed between urologists (0.31). CONCLUSIONS: The study demonstrates poor intra- and inter-observer reliability of the CSE. According to these results, a CSE does not add valuable information to the clinical evaluation. In this scenario, it should not be considered in isolation from the patient's characteristics.

VaNoLaH trial: a study protocol-a multinational randomised controlled trial including two identical substudies comparing vaginal versus vNOTES (vaginal natural orifice transluminal surgery) hysterectomy or laparoscopic versus vNOTES hysterectomy.

INTRODUCTION: Hysterectomy is one of the most common surgeries performed in women. Minimally invasive methods are on the rise globally as they have been shown to decrease surgical morbidity compared with abdominal hysterectomy. Hysterectomy by vaginal natural orifice transluminal endoscopic surgery (vNOTES) is the latest innovation. It combines the vaginal approach and endoscopy via the vagina. Large pragmatic randomised controlled trials (RCTs) are lacking comparing outcomes after vNOTES, vaginal hysterectomy (VH) and laparoscopic hysterectomy (LH). METHODS: Multicentre pragmatic RCT aiming to recruit 1000 women aged 18-75 years undergoing hysterectomy for benign disease. The RCT includes two identical substudies (groups A and B). If VH is considered safe and feasible, the patient will be randomised within group A (VH vs vNOTES). If VH is not considered safe or feasible, patients will be randomised within group B (LH vs vNOTES). ANALYSIS: Primary outcome is the proportion of women leaving the hospital within 12 hours after surgery. Secondary outcomes are hospitalisation time, conversion rates, duration of the surgical procedure, intraoperative complications, postoperative complications and readmission. ETHICS AND DISSEMINATION: The Ethical Board Committee at Imelda Hospital, Bonheiden, Belgium, has approved the research protocol 230704 (principal investigator). Before including patients, all centres will require local or national ethical approval. The results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05971875.

The prognostic effect of radiological extranodal extension in HPV-positive oropharyngeal squamous cell carcinomas: a retrospective cohort analysis.

PURPOSE: Radiological extranodal extension (rENE) is a well-known negative prognosticator in head and neck squamous cell carcinoma (HNSCC). However, controversy remains regarding the prognostic effect of rENE in HPV-positive oropharyngeal SCCs (OPSCC). This single-center retrospective cohort analysis assessed the prognostic role of rENE in an HPV + OPSCC population and tried to validate a recently proposed modification of the TNM8 N-classification. METHODS: 129 patients with HPV + OPSCC, of whom 106 cN + patients, were included. Radiological imaging (CT, MRI or both) was reanalyzed by a senior head and neck radiologist. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS), and disease-specific survival (DSS) were evaluated. Cox proportional hazard models were used for estimating hazard ratios (HR). RESULTS: A non-significant trend towards better outcomes in the rENE- group, as compared to the rENE + population, was observed for 5 year OS [80.99% vs 68.70%, HR: 2.05, p = 0.160], 5 year RFS [78.81% vs 67.87%, HR: 1.91, p = 0.165], 5 year DFS [77.06% vs 60.16%, HR: 2.12, p = 0.0824] and 5 year DSS [88.83% vs 81.93%, HR: 2.09, p = 0.195]. OS declined with ascending levels of rENE (p = 0.020). Multivariate analysis identified cT-classification and smoking as independent negative predictors for OS/DFS. The proposed modification of the TNM8 N-classification could not be validated. CONCLUSIONS: Although rENE could not be identified as an independent negative prognosticator for outcome in our HPV + OPSCC population, outcomes tend to deteriorate with increasing rENE.

Prospective Evaluation and Validation of the Laryngoscore and the mini-Laryngoscore.

OBJECTIVE: The Laryngoscore was described in 2014 as a practical preoperative assessment tool to predict difficult laryngeal exposure (DLE) during transoral approaches to the larynx. In 2019 the authors proposed a version with a reduced number of variables, called the mini-Laryngoscore. We aim to critically appraise and externally validate these two tools and if needed and possible, to optimize these tools. METHODS: 103 consecutive patients who underwent a microlaryngoscopy between November 2017 and June 2020 at the Leuven University Hospitals were prospectively included and subjected to a presurgical evaluation of 15 parameters and a peroperative scoring of the anterior commissure visualization. Subsequent analysis focused on the concordance of our findings with those of Piazza et al., the discriminatory ability of the test, and the validity of the included items. We then evaluated a modified prediction tool. RESULTS: Of 103 patients, 18 (17.5%) had DLE. The Laryngoscore and mini-Laryngoscore predicted this with a "good" C-index of respectively 0.727 (95%CI: 0.608-0.846) and 0.714 (95%CI: 0.605-0.823). A newly created prediction tool including only three parameters (Interincisors gap, upper jaw dental status and previous treatments) showed a better discriminatory ability (C-index = 0.835, 95%CI: 0.726-0.944) than the original Laryngoscore, a finding that needs further external validation. CONCLUSION: The original Laryngoscore and the mini-Laryngoscore displayed a good discriminative ability. Some parameters can be left out of the Laryngoscore without losing discrimination. An even better prediction model seems possible, using a weighted sum of selected predictor variables and by using the parameters in their continuous form. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:1807-1812, 2024.

Intra-individual qualitative and quantitative comparison of [68Ga]Ga-DOTATATE PET/CT and PET/MRI.

Background: Somatostatin receptor (SSTR) positron emission tomography (PET) is a cornerstone of neuroendocrine tumor (NET) management. Hybrid PET/magnetic resonance imaging (MRI) is now available for NET-imaging, next to PET/computed tomography (CT). Objectives: To determine whether CT or MRI is the best hybrid partner for [68Ga]Ga-DOTATATE PET. Design: Monocentric, prospective study. Methods: Patients received a same-day [68Ga]Ga-DOTATATE PET/CT and subsequent PET/MRI, for suspicion of NET, (re)staging or peptide receptor radionuclide therapy-selection. The union (PETunion) of malignant lesions detected on PETCT and PETMRI was the reference standard. Concordance of detection of malignant lesions in an organ was measured between PETunion and CT and PETunion and MRI. Seven bins were used to categorize the number of malignant lesions, containing following ordinal variables: 0, 1, 2-5, 6-10, 11-20, >20 countable and diffuse/uncountable. The difference in number of malignant lesions was obtained as the difference in bin level ('Δbin') between PETunion and CT and PETunion and MRI with a Δbin closer to zero implying a higher concordance rate. Results: Twenty-nine patients were included. Primary tumors included 17 gastroenteropancreatic-NETs, 1 colon neuroendocrine carcinoma, 7 lung-NETs and 2 meningiomas. Patient level concordance with PETunion was 96% for MRI and 67% for CT (p = 0.039). Organ level concordance with PETunion was 74% for MRI and 40% for CT (p < 0.0001). In bone, there was a higher concordance rate for MRI compared to CT, 92% and 33%, respectively (p = 0.016). Overall, a mean Δbin of 0.5 ± 1.1 for PETunion/MRI and 1.4 ± 1.2 for PETunion/CT (p < 0.0001) was noted. In liver, a mean Δbin of 0.0 ± 1.1 for PETunion/MRI and 1.7 ± 1.2 for PETunion/CT was observed (p = 0.0078). In bone, a mean Δbin closer to zero was observed for PETunion/MRI compared to PETunion/CT, 0.6 ± 1.4 and 2.0 ± 1.5, respectively (p = 0.0098). Conclusions: Compared to SSTR PET/CT, SSTR PET/MRI had a higher patient and organ level concordance for malignant tumoral involvement and number of malignant lesions, with a clear added value in bone and liver specifically.

Circulating biomarkers at diagnosis correlate with distant metastases of early luminal-like breast cancer.

There is an urgent need for new and better biomarker modalities to estimate the risk of recurrence within the luminal-like breast cancer (BC) population. Molecular diagnostic tests used in the clinic lack accuracy in identifying patients with early luminal BC who are likely to develop metastases. This study provides proof of concept that various liquid biopsy read-outs could serve as valuable candidates to build a multi-modal biomarker model distinguishing, already at diagnosis, between early metastasizing and non-metastasizing patients. All these blood biomarkers (chemokines, microRNAs, leukemia inhibitory factor, osteopontin, and serum-induced functional myeloid signaling responses) can be measured in baseline plasma/serum samples and could be added to the existing prognostic factors to improve risk stratification and more patient-tailored treatment in early luminal BC.

Prospective comparison of [18F]AlF-NOTA-octreotide PET/MRI to [68Ga]Ga-DOTATATE PET/CT in neuroendocrine tumor patients.

BACKGROUND: Fluorine-18-labeled SSAs have the potential to become the next-generation tracer in SSTR-imaging in neuroendocrine tumor (NET) patients given their logistical advantages over the current gold standard gallium-68-labeled SSAs. In particular, [18F]AlF-OC has already shown excellent clinical performance. We demonstrated in our previous report from our prospective multicenter trial that [18F]AlF-OC PET/CT outperforms [68Ga]Ga-DOTA-SSA, but histological confirmation was lacking due to ethical and practical reasons. In this second arm, we therefore aimed to provide evidence that the vast majority of [18F]AlF-OC PET lesions are in fact true NET lesions by analyzing their MR characteristics on simultaneously acquired MRI. We had a special interest in lesions solely detected by [18F]AlF-OC ("incremental lesions"). METHODS: Ten patients with a histologically confirmed neuroendocrine tumor (NET) and a standard-of-care [68Ga]Ga-DOTATATE PET/CT, performed within 3 months, were prospectively included. Patients underwent a whole-body PET/MRI (TOF, 3 T, GE Signa), 2 hours after IV injection of 4 MBq/kg [18F]AlF-OC. Positive PET lesions were evaluated for a corresponding lesion on MRI. The diagnostic performance of both PET tracers was evaluated by determining the detection ratio (DR) for each scan and the differential detection ratio (DDR) per patient. RESULTS: In total, 195 unique lesions were detected: 167 with [68Ga]Ga-DOTATATE and 193 with [18F]AlF-OC. The DR for [18F]AlF-OC was 99.1% versus 91.4% for [68Ga]Ga-DOTATATE, significant for non-inferiority testing (p = 0.0001). Out of these 193 [18F]AlF-OC lesions, 96.2% were confirmed by MRI to be NET lesions. Thirty-three incremental lesions were identified by [18F]AlF-OC, of which 91% were confirmed by MRI and considered true positives. CONCLUSION: The DR of [18F]AlF-OC was numerically higher and non-inferior to the DR of [68Ga]Ga-DOTATATE. [18F]AlF-OC lesions and especially incremental lesions were confirmed as true positives by MRI in more than 90% of lesions. Taken together, these data further validate [18F]AlF-OC as a new alternative for SSTR PET in clinical practice. Trial registration ClinicalTrials.gov: NCT04552847. Registered 17 September 2020, https://beta. CLINICALTRIALS: gov/study/NCT04552847.

Comparison of Clinical Performance Between Two Types of Symmetric-Tip Hemodialysis Catheters: A Single-Centre, Randomized Trial.

PURPOSE: To compare the clinical performance of a newly designed, symmetric-tip Arrow-Clark™ VectorFlow® tunnelled haemodialysis catheter, with a Glidepath™, symmetric-tip tunnelled haemodialysis catheter. MATERIAL AND METHODS: From November 2018 to October 2020, patients with End-Stage Renal Disease requiring a de novo tunnelled catheter for hemodialysis, were randomized to Vectorflow® (n = 50) or to Glidepath™ catheter (n = 48). The primary outcome was catheter patency at one year following catheter insertion. Catheter failure was defined as the removal of the catheter due to infectious complications, or low blood flow rate by intraluminal thrombosis or fibrin sheath occlusion. Secondary outcomes were blood flow rate, fractional urea clearance and urea reduction ratio during dialysis. RESULTS: Demographic characteristics were not different between the two groups. At three months and on the one-year endpoint the patency rates with the Vectorflow® catheter were 95.83% and 83.33% respectively, compared to 93.02% at both endpoints with the Glidepath™ catheter (P = 0.27). Catheter failure to infectious complications or low blood flow rate was similar in both groups. Catheter blood flow rate reached the threshold of 300 ml/min at all time points for both catheters. All patients had a high mean fractional urea clearance (1.6-1.7). CONCLUSIONS: The catheter patency rate was not significantly different in patients with a VectorFlow® or a Glidepath™ catheter. Both catheters presented satisfactory dialysis adequacy over one year.

Role of immune checkpoint inhibitors in metastatic uveal melanoma: a single-center retrospective cohort study.

BACKGROUND: Uveal melanoma is an orphan malignancy with very limited data on treatment options in metastatic setting. METHODS: In this single-center retrospective study, we describe real-world epidemiological and survival data on 121 metastatic uveal melanoma (MUM) patients registered in our institution. As a large tertiary referral center, almost 30% of all diagnoses in the Flemish region of Belgium were covered. Primarily, we determined whether introduction of immune checkpoint inhibitors (ICI) led to improved overall survival (OS) in MUM patients. Secondarily, response rates to ICI were assessed and we evaluated whether first-line ICI could be a valid alternative to liver-directed therapy (LDT) in liver-only disease. RESULTS: The initially perceived 10.8 months survival benefit from treatment with ICI disappeared after correction for immortality bias. By analyzing treatment type as time-varying covariate on OS, no significant benefit of ICI over other systemic therapies (HR = 0.771) or best supportive care (BSC) (HR = 0.780) was found. Also comparison of the pre-ICI versus ICI era showed no OS improvement after introduction of ICI in our center (p = 0.7994). Only liver-directed and local oligometastatic approaches were associated with a lower chance of mortality when compared to ICI (p = 0.0025), other systemic therapies (p = 0.0001) and BSC (p = 0.0003), yet without correction for selection bias. We reported overall response rates on ICI ranging from 8-15% and we found some support for neoadjuvant strategies with ICI resulting in remission or downsizing, allowing oligometastatic approaches later on. In first-line liver-only disease, median real-world progression-free survival and OS did not significantly differ between patients treated with LDT or ICI upfront (p = 0.2930 and p = 0.5461 respectively). CONCLUSION: Although we documented responses to ICI, our analyses do not demonstrate an OS benefit of ICI over alternative treatment strategies for MUM. However, local treatment options, whether liver-directed or for oligometastatic disease, may be beneficial and should be considered.

Coronary covered stents in the management of late-onset arterial complications post-hepato-pancreato-biliary surgery.

PURPOSE: To retrospectively evaluate the safety, efficacy, and late clinical outcome of coronary covered stent placement for the treatment of late-onset arterial complications after hepato-pancreato-biliary surgery. MATERIALS AND METHODS: Consecutive patients presenting with post-hepato-pancreato-biliary surgery-related arterial lesions and subsequently treated with a covered coronary stent in the authors institution between January 2012 and November 2021 were included. Primary endpoints were technical and clinical success; secondary endpoints were covered stent patency and end-organ perfusion of the affected artery. RESULTS: The study included 22 patients (13 men and 9 women) with a mean age of 67 years ± 9.6 years. Initial surgery included pancreaticoduodenectomy (n = 15; 68%), liver transplantation (n = 2; 9%), left hepatectomy (n = 1; 5%), bile duct resection (n = 1; 5%), hepatogastrostomy (n = 1; 5%), and segmental enterectomy (n = 1; 5%). Technically, coronary covered stents were successfully placed in n = 22 patients (100%) without immediate complication. Definitive bleeding control was observed in n = 18 patients (81.1%) with recurrent bleeding within 30 days postintervention in n = 5 patients (23%). No ischemic liver or biliary complications occurred during the follow-up period. The 30-day mortality rate was 0%. CONCLUSION: Coronary covered stents are a safe and efficient treatment option in most of the patients presenting with late-onset postoperative arterial injuries following hepato-pancreato-biliary surgery and are associated with an acceptable recurrent bleeding rate and no late, ischemic, parenchymal complications.

Improving Endometrial cancer assessment by combining the new techniqUe of GENomic profiling with surgical Extra uterIne disEase assessment (EUGENIE).

BACKGROUND: The molecular classification of endometrial cancer revolutionized our knowledge of its biology but so far has not affected our surgical approach. The exact risk of extra-uterine metastasis and hence the type of surgical staging for each of the four molecular subgroups are currently unknown. PRIMARY OBJECTIVE: To determine the association between molecular classification and disease stage. STUDY HYPOTHESIS: Each endometrial cancer molecular subgroup has a specific pattern of spread and this pattern of spread could guide the extent of surgical staging. TRIAL DESIGN: Prospective, multicenter study MAJOR INCLUSION/EXCLUSION CRITERIA: Participants eligible for inclusion in this study must meet all the following criteria: women ≥18 years with primary endometrial cancer, any histology and stage. PRIMARY ENDPOINT: Number and site of metastasis in each endometrial cancer molecular subgroup. SAMPLE SIZE: 1000 patients will be enrolled. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The trial will last 6 years: 4 years of accrual, and 2 years of follow-up of all patients. Results on staging and oncological outcomes are expected in 2027 and 2029, respectively. TRIAL REGISTRATION: The study has been accepted by UZ Leuven Ethical Committee. Belg. Reg. nr: B3222022000997.

[18F]FDG-PET/CT volumetric parameters can predict outcome in untreated mantle cell lymphoma.

Several studies have shown a strong predictive value for pretreatment [18F]FDG-PET/CT metabolic parameters in different lymphoma subtypes. However, few publications exist concerning the role of metabolic parameters in mantle cell lymphoma (MCL). We retrospectively investigated the prognostic value of baseline metabolic tumor volume (MTV) and lesion dissemination in untreated MCL. We compared it to currently used prognostic factors such as stage, mantle cell lymphoma international prognostic index (MIPI) and KI-67. We report that a higher baseline MTV is a risk factor for worse overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) in univariate analysis. In multivariate analysis, MTV was significantly associated with DSS, but not with OS and PFS. We found no correlation between lesion dissemination and outcome. The MIPI score remains the strongest predictor of outcome. These results show that MTV is an important prognostic tool and can improve patient risk stratification at staging of untreated MCL.

Predicting short- and long-term renal function following partial and radical nephrectomy.

OBJECTIVES: To externally validate the previously published Mayo clinic model for the prediction of early (<30 days) postoperative renal failure, which relies solely on preoperative estimated glomerular filtration rate (eGFR) and develop a novel model for the prediction of long-term (>30 days) renal function after partial nephrectomy (PN) and radical nephrectomy (RN), including patient factors and nephrometry scores. PATIENTS AND METHODS: Retrospective, single-center cohort study on patients who underwent PN or RN for a unilateral renal tumor between 2003 and 2019 with a preoperative eGFR of at least 15 ml/min/1.73m2. Early postoperative renal failure was defined as eGFR <15 ml/min/1.73 m2 or receipt of dialysis within 30 days. We determined the area under the receiver operating characteristics curve (AUC) to assess the Mayo clinic model's discriminative power. We used hierarchical linear mixed models with backward selection of candidate variables to develop a prediction model for long-term eGFR following PN and RN, separately. Their predictive ability was quantified using the marginal and conditional R2GLMM and an internal validation. RESULTS: We included 421 patients (7,548 eGFR observations) who underwent PN and 271 patients (6,530 eGFR observations) who underwent RN. The Mayo clinic model for prediction of early postoperative renal failure following PN and RN showed an AUC of 0.816 (95% CI 0.718-0.920) and 0.825 (95% CI 0.688-0.962), respectively. In multivariable models, long-term eGFR following PN was associated with age, diabetes, the presence of a solitary kidney, tumor diameter and preoperative eGFR, while long-term eGFR following RN was associated with age, body mass index, RENAL nephrometry score and preoperative eGFR. Marginal and conditional R2GLMM were 0.591 and 0.855 for the PN model, and 0.363 and 0.849 for the RN model, respectively. CONCLUSIONS: The Mayo clinic model for short-term renal failure prediction showed good accuracy on external validation. Our long-term eGFR prediction models depend mostly on host factors as opposed to tumor complexity and can aid in decision-making when considering PN vs. RN.

18F-AlF-NOTA-Octreotide Outperforms 68Ga-DOTATATE/NOC PET in Neuroendocrine Tumor Patients: Results from a Prospective, Multicenter Study.

18F-labeled somatostatin analogs (SSAs) could represent a valid alternative to the current gold standard, 68Ga-labeled SSAs, for somatostatin receptor imaging in patients with neuroendocrine tumors (NETs), given their logistic advantages. Recently, 18F-AlF-NOTA-octreotide (18F-AlF-OC) has emerged as a promising candidate, but a thorough comparison with 68Ga-DOTA-SSA in large patient groups is needed. This prospective, multicenter trial aims to demonstrate noninferiority of 18F-AlF-OC compared with 68Ga-DOTA-SSA PET in NET patients (ClinicalTrials.gov, NCT04552847). Methods: Seventy-five patients with histologically confirmed NET and routine clinical 68Ga-DOTATATE (n = 56) or 68Ga-DOTANOC (n = 19) PET, performed within a 3-mo interval of the study scan (median, 7 d; range, -30 to +32 d), were included. Patients underwent a whole-body PET 2 h after intravenous injection of 4 MBq/kg of 18F-AlF-OC. A randomized, masked consensus read was performed by 2 experienced readers to count tumor lesions. After unmasking, the detection ratio (DR) was determined for each scan, that is, the fraction of lesions detected on a scan compared with the union of lesions of both scans. The differential DR (DDR; difference in DR between 18F-AlF-OC and 68Ga-DOTATATE/NOC) per patient was calculated. Tracer uptake was evaluated by comparing SUVmax and tumor-to-background ratios in concordant lesions. Results: In total, 4,709 different tumor lesions were detected: 3,454 with 68Ga-DOTATATE/NOC and 4,278 with 18F-AlF-OC. The mean DR with 18F-AlF-OC was significantly higher than with 68Ga-DOTATATE/NOC (91.1% vs. 75.3%; P < 10-5). The resulting mean DDR was 15.8%, with a lower margin of the 95% CI (95% CI, 9.6%-22.0%) higher than -15%, which is the prespecified boundary for noninferiority. The mean DDRs for the 68Ga-DOTATATE and 68Ga-DOTANOC subgroups were 11.8% (95% CI, 4.3-19.3) and 27.5% (95% CI, 17.8-37.1), respectively. The mean DDR for most organs was higher than zero, except for bone lesions (mean DDR, -2.8%; 95% CI, -17.8 to 12.2). No significant differences in mean SUVmax were observed (P = 0.067), but mean tumor-to-background ratio was significantly higher with 18F-AlF-OC than with 68Ga-DOTATATE/NOC (31.7 ± 36.5 vs. 25.1 ± 32.7; P = 0.001). Conclusion: 18F-AlF-OC is noninferior and even superior to 68Ga-DOTATATE/NOC PET in NET patients. This validates 18F-AlF-OC as an option for clinical practice somatostatin receptor PET.

Blended care to discontinue benzodiazepine receptor agonists use in patients with chronic insomnia disorder: a pragmatic cluster randomized controlled trial in primary care.

STUDY OBJECTIVES: International guidelines recommend using benzodiazepine receptor agonists (BZRA) for maximally four weeks. Nevertheless, long-term use for chronic insomnia disorder remains a common practice. This study aimed to test the effectiveness of blended care for discontinuing long-term BZRA use in general practice. METHODS: A pragmatic cluster randomized controlled superiority trial compared blended care to usual care through urine toxicology screening. In the intervention, care by the general practitioner (GP) was complemented by an interactive e-learning program, based on cognitive behavioral therapy for insomnia. Adults using BZRA daily for minimally 6 months were eligible. Participants were clustered at the level of the GP surgery for allocation (1:1). Effectiveness was measured as the proportion of patients who had discontinued at one-year follow-up. Data analysis followed intention-to-treat principles. RESULTS: In total, 916 patients in 86 clusters, represented by 99 GPs, were randomized. Primary outcome data was obtained from 727 patients (79%). At one-year follow-up, 82 patients (18%) in blended care, compared to 91 patients (20%) in usual care, had discontinued. There was no statistically significant effect for the intervention (OR: 0.924; 95% CI: 0.60; 1.43). No adverse events were reported to the research team. CONCLUSIONS: The findings did not support the superiority of blended care over usual care. Both strategies showed clinical effectiveness, with an average of 19% of patients having discontinued at one-year follow-up. Further research is important to study the effect of structurally implementing digital interventions in general practice. CLINICAL TRIAL: Big Bird trial; KCE-17016. This trial is registered at clinicaltrials.gov (NCT03937180).

Safety, Efficacy, and Predictors for Late Reintervention After Embolization of Renal Angiomyolipomas - Embolization renal angiomyolipoma.

PURPOSE: To retrospectively analyze the procedural and long-term clinical outcome of the selective embolization of renal angiomyolipoma. In addition, potential predictive factors for higher risk of late re-intervention were analyzed. METHODS: Retrospective monocentric study, including 34 consecutive patients, analyzing the safety, efficiency, and long-term clinical outcome of catheter-directed embolization of renal AML. Additionally, the difference in postembolization renal function between patients embolized in the acute and in the elective setting was analyzed. Secondly, we also evaluated whether volume/diameter of the AML and presence of intralesional aneurysms are risk factors for late re-intervention. RESULTS: Embolization of renal AML was performed to control volume (n = 21; 62 %) or to stop spontaneous hemorrhage (n = 13; 38 %) with angiographic success in all cases but was associated with renal abscess (n = 1) and pulmonary embolism (n = 1) without a significant difference in renal function before and after embolization (P = 0.513). Volume/diameter (P = 0.276/P = 0.21) and presence of aneurysms before embolization (P = 0.37) are not predictive for a higher risk of late re-intervention. CONCLUSION: Catheter-directed embolization is a safe and effective treatment modality for asymptomatic and bleeding renal AML, without a negative impact on renal function. Initial mass volume/diameter or presence/absence of intralesional aneurysms does not seem to be predictive for late re-intervention. KEY POINTS: · Complications related to renal angiomyolipoma embolization are rare.. · Embolization of angiomyolipoma will not reduce renal function.. · Initial volume or diameter of angiomyolipoma is not predictive for late re-intervention.. CITATION FORMAT: · Claesen E, Bonne L, Laenen A et al. Safety, Efficacy, and Predictors for Late Reintervention After Embolization of Renal Angiomyolipomas. Fortschr Röntgenstr 2023; 195: 319 - 325.

ARNEO: A Randomized Phase II Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer.

BACKGROUND: High-risk prostate cancer (PCa) patients have a high risk of biochemical recurrence and metastatic progression following radical prostatectomy (RP). OBJECTIVE: To determine the efficacy of neoadjuvant degarelix plus apalutamide before RP compared with degarelix with a matching placebo. DESIGN, SETTING, AND PARTICIPANTS: ARNEO was a randomized, placebo-controlled, phase II neoadjuvant trial before RP performed between March 2019 and April 2021. Eligible patients had high-risk PCa and were amenable to RP. INTERVENTION: Patients were randomly assigned at a 1:1 ratio to degarelix (240-80-80 mg) + apalutamide (240 mg/d) versus degarelix + matching placebo for 3 mo followed by RP. Prior to and following neoadjuvant treatment, pelvic 18F-PSMA-1007 positron emission tomography (PET)/magnetic resonance imaging (MRI) was performed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the difference in proportions of patients with minimal residual disease (MRD; = residual cancer burden (RCB) ≤0.25 cm3 at final pathology). Secondary endpoints included differences in prostate-specific antigen responses, pathological staging, and change in TNM stage on prostate-specific membrane antigen (PSMA) PET/MRI following hormonal treatment. Biomarkers (immunohistochemical staining on prostate biopsy [PTEN, ERG, Ki67, P53, GR, and PSMA] and PSMA PET/MRI-derived characteristics) associated with pathological response (MRD and RCB) were explored. RESULTS AND LIMITATIONS: Patients were randomized to neoadjuvant degarelix + apalutamide (n = 45) or degarelix + matching placebo (n = 44) for 12 wk and underwent RP. Patients in the degarelix + apalutamide arm achieved a significantly higher rate of MRD than those in the control arm (38% vs 9.1%; relative risk [95% confidence interval] = 4.2 [1.5-11], p = 0.002). Patients with PTEN loss in baseline prostate biopsy attained significantly less MRD (11% vs 43%, p = 0.002) and had a higher RCB at final pathology (1.6 vs 0.40 cm3, p < 0.0001) than patients without PTEN loss. Following neoadjuvant hormonal therapy, PSMA PET-estimated tumor volumes (1.2 vs 2.5 ml, p = 0.01) and maximum standardized uptake value (SUVmax; 4.3 vs 5.7, p = 0.007) were lower in patients with MRD than in patients without MRD. PSMA PET-estimated volume and PSMA PET SUVmax following neoadjuvant treatment correlated significantly with RCB at final pathology (both p < 0.001). CONCLUSIONS: In high-risk PCa patients, neoadjuvant degarelix plus apalutamide prior to RP results in a significantly improved pathological response (MRD and RCB) compared with degarelix alone. Our trial results provide a solid hypothesis-generating basis for neoadjuvant phase 3 trials, which are powered to detect differences in long-term oncological outcome following neoadjuvant androgen receptor signaling inhibitor therapy. PATIENT SUMMARY: In this study, we looked at the difference in pathological responses in high-risk prostate cancer patients treated with degarelix plus apalutamide or degarelix plus matching placebo prior to radical prostatectomy. We demonstrated that patients treated with degarelix plus apalutamide achieved a significantly better tumor response than patients treated with degarelix plus matching placebo. Long-term follow-up is required to determine whether improved pathological outcome translates into better oncological outcomes.

Retrospective Cohort Study of Practical Applications of Paramagnetic Seed Localisation in Breast Carcinoma and Other Malignancies.

(1) Background: Paramagnetic seeds are a safe alternative for the wire-guided localisation of non-palpable breast lesions, but can also be applied for non-breast lesions. This study presents the experience with a paramagnetic seed, MagSeed® (Endomagnetics Ltd., Cambridge, UK, CE-registered and FDA-cleared), in an academic and non-academic breast centre. (2) Methods: Multicentre, retrospective analysis of 374 consecutive patients who underwent surgery after paramagnetic seed localisation (MSL) between 2018 and 2020. Indications for localisation included non-palpable breast lesions (n = 356), lymph nodes (n = 15) or soft tissue lesions (n = 3). The primary outcome was feasibility and the rate of positive section margins. The secondary outcome was predictive factors for positive section margins. (3) Results: The accurate excision of high-risk breast lesions, lymph nodes and soft tissue lesions was seen in 91.07% (n = 56). Positive section margins were observed in 7.86% (n = 25) after breast conserving surgery for invasive or ductal carcinoma in situ (DCIS) (n = 318). Invasive breast cancer associated with DCIS (p = 0.043) and the size of DCIS (p < 0.001) were significantly correlated with the positive section margins. (4) Conclusion: This study confirms the feasibility of MSL, as well as the higher risk for positive margins in cases of breast carcinoma with associated DCIS. Soft tissue lesions and lymph nodes associated with other malignancies, e.g., melanoma, can also be localised with paramagnetic seeds. This offers perspectives for future applications, such as the de-escalation of axillary treatment in breast cancer.

Correlation of TROP-2 expression with clinical-pathological characteristics and outcome in triple-negative breast cancer.

Limited data exist regarding the associations between TROP-2 protein expression, clinical-pathological characteristics, and outcome in triple-negative breast cancer (TNBC). TROP-2 expression was determined for patients diagnosed with TNBC between 2000 and 2017 by immunohistochemistry (IHC) (ab227689, Abcam) on whole slide tumor sections, and assessed as continuous and categorical variables (H-score high, 201-300, medium 100-200 and low < 100). We investigated the prognostic value of TROP-2 expression for relapse and survival, associations between TROP-2 expression and baseline patient and tumor characteristics, stromal tumor-infiltrating lymphocytes (sTILs), androgen receptor (AR), standardized mitotic index (SMI) and pathological complete response (pCR, in patients with neoadjuvant chemotherapy) were assessed. We included 685 patients with a median age at diagnosis of 54 years (range 22-90 years). After median follow-up of 9.6 years, 17.5% of patients experienced distant relapse. TROP-2 expression was high, medium and low in 97 (16.5%), 149 (25.3%) and 343 (58.2%) of patients, respectively. The presence of LVI, associated DCIS, nodal involvement, apocrine histology and AR expression were correlated with higher TROP-2 levels. There were no associations between TROP-2 expression and sTILs, time-to-event outcomes, or pCR rate after neoadjuvant chemotherapy. TROP-2 expression is not associated with sTILs level and has no prognostic value in our cohort of stage 1-3 TNBC. However, an association with histotype and AR expression was found, suggesting a histotype specific TROP-2 expression pattern with highest expression in apocrine subtype, warranting further research.