Prospective Validation Research Articles

Improving computerized decision support system interventions: a qualitative study combining the theoretical domains framework with the GUIDES Checklist

BackgroundComputerized clinical decision support systems (CDSSs) can improve care by bridging knowledge to practice gaps. However, the real-world uptake of such systems in health care settings has been suboptimal. We sought to: (1) use the Theoretical Domains Framework (TDF) to identify determinants (barriers/enablers) of uptake of the Electronic Asthma Management System (eAMS) CDSS; (2) match identified TDF belief statements to elements in the Guideline Implementation with Decision Support (GUIDES) Checklist; and (3) explore the relationship between the TDF and GUIDES frameworks and the usefulness of this sequential approach for identifying opportunities to improve CDSS uptake.MethodsIn Phase 1, we conducted semistructured interviews with primary care physicians in Toronto, Canada regarding the uptake of the eAMS CDSS. Using content analysis, two coders independently analyzed interview transcripts guided by the TDF to generate themes representing barriers and enablers to CDSS uptake. In Phase 2, the same reviewers independently mapped each belief statement to a GUIDES domain and factor. We calculated the proportion of TDF belief statements that linked to each GUIDES domain and the proportion of TDF domains that linked to GUIDES factors (and vice-versa) and domains.ResultsWe interviewed 10 participants before data saturation. In Phase 1, we identified 53 belief statements covering 12 TDF domains; 18 (34.0%) were barriers, and 35 (66.0%) were enablers. In Phase 2, 41 statements (77.4%) linked to at least one GUIDES factor, while 12 (22.6%) did not link to any specific factor. The GUIDES Context Domain was linked to the largest number of belief statements (19/53; 35.8%). Each TDF domain linked to one or more GUIDES factor, with 6 TDF domains linking to more than 1 factor and 8 TDF domains linking to more than 1 GUIDES domain.ConclusionsThe TDF provides unique insights into barriers and enablers to CDSS uptake, which can then be mapped to GUIDES domains and factors to identify required changes to CDSS context, content, and system. This can be followed by conventional mapping of TDF domains to behaviour change techniques to optimize CDSS implementation. This novel step-wise approach combines two established frameworks to optimize CDSS interventions, and requires prospective validation.

Validation and update of a clinical score model to predict technical difficulty of colorectal endoscopic submucosal dissection: a multicenter prospective cohort study

Background and AimsThe Zhongshan CR-ESD Score model was proposed to grade the technical difficulty of colorectal endoscopic submucosal dissection (CR-ESD). The objective of this study is to prospectively validate and update the score model. MethodsA multicenter prospective cohort analysis of CR-ESD was conducted. Individual data on patients, lesions, and outcomes of CR-ESD were utilized to validate the original model and further refine the difficulty prediction model. The data was randomly divided into discovery and internal validation cohorts. A multivariate Cox regression analysis was conducted on the discovery cohort to develop an updated risk-scoring system, which was then validated. ResultsA total of 548 patients with 565 colorectal lesions treated by ESD from 4 hospitals were included. In the prospective validation cohort, the area under the receiver operating characteristic (ROC) curve for the original model was 0.707. Six risk factors were identified and assigned point values: tumor size (2 points for 30-50 mm, 3 points for ≥50 mm), ≥ 2/3 circumference of the lesion (3 points), tumor location in the cecum (2 points) or flexure (2 points), LST-NG lesions (1 point), preceding biopsy (1 point), and NICE type3 (3 points). In the discovery cohort, the updated model had an area under the ROC curve of 0.738, while in the validation cohort it was 0.782. The cases were categorized into easy (score = 0-1), intermediate (score = 2-3), difficult (score = 4-6), and very difficult (score ≥7) groups. Satisfactory discrimination and calibration were observed. ConclusionsThe original model achieved an acceptable level of prediction in the prospective cohort. The updated model exhibited superior performance and can be used in place of the previous version.

Six-Lead Electrocardiography Enables Identification of Rhythm and Conduction Anomalies of Patients in the Telemedicine-Based, Hospital-at-Home Setting: A Prospective Validation Study.

The hospital-at-home (HAH) model is a viable alternative for conventional in-hospital stays worldwide. Serum electrolyte abnormalities are common in acute patients, especially in those with many comorbidities. Pathologic changes in cardiac electrophysiology pose a potential risk during HAH stays. Periodical electrocardiogram (ECG) tracing is therefore advised, but few studies have evaluated the accuracy and efficiency of compact, self-activated ECG devices in HAH settings. This study aimed to evaluate the reliability of such a device in comparison with a standard 12-lead ECG. We prospectively recruited consecutive patients admitted to the Sheba Beyond Virtual Hospital, in the HAH department, during a 3-month duration. Each patient underwent a 12-lead ECG recording using the legacy device and a consecutive recording by a compact six-lead device. Baseline patient characteristics during hospitalization were collected. The level of agreement between devices was measured by Cohen's kappa coefficient for inter-rater reliability (Ϗ). Fifty patients were included in the study (median age 80 years, IQR 14). In total, 26 (52%) had electrolyte disturbances. Abnormal D-dimer values were observed in 33 (66%) patients, and 12 (24%) patients had elevated troponin values. We found a level of 94.5% raw agreement between devices with regards to nine of the options included in the automatic read-out of the legacy device. The calculated Ϗ was 0.72, classified as a substantial consensus. The rate of raw consensus regarding the ECG intervals' measurement (PR, RR, and QT) was 78.5%, and the calculated Ϗ was 0.42, corresponding to a moderate level of agreement. This is the first report to our knowledge regarding the feasibility of using a compact, six-lead ECG device in the setting of an HAH to be safe and bearing satisfying agreement level with a legacy, 12-lead ECG device, enabling quick, accessible arrythmia detection in this setting. Our findings bear a promise to the future development of telemedicine-based hospital-at-home methodology.

"Soap bubble" sign as an imaging marker for posterior fossa ependymoma Group B.

To investigate the predictive value of the "soap bubble" sign on molecular subtypes (Group A [PFA] and Group B [PFB]) of posterior fossa ependymomas (PF-EPNs). MRI scans of 227 PF-EPNs (internal retrospective discovery set) were evaluated by two independent neuroradiologists to assess the "soap bubble" sign, which was defined as clusters of cysts of various sizes that look like "soap bubbles" on T2-weighted images. Two independent cohorts (external validation set [n = 31] and prospective validation set [n = 27]) were collected to validate the "soap bubble" sign. Across three datasets, the "soap bubble" sign was observed in 21 PFB cases (7.4% [21/285] of PF-EPNs and 12.9% [21/163] of PFB); none in PFA. Analysis of the internal retrospective discovery set demonstrated substantial interrater agreement (1st Rating: κ = 0.71 [0.53-0.90], 2nd Rating: κ = 0.83 [0.68-0.98]) and intrarater agreement (Rater 1: κ = 0.73 [0.55-0.91], Rater 2: κ = 0.74 [0.55-0.92]) for the "soap bubble" sign; all 13 cases positive for the "soap bubble" sign were PFB (p = 0.002; positive predictive value [PPV] = 100%, negative predictive value [NPV] = 44%, sensitivity = 10%, specificity = 100%). The findings from the external validation set and the prospective validation set were similar, all cases positive for the "soap bubble" sign were PFB (p < 0.001; PPV = 100%). The "soap bubble" sign represents a highly specific imaging marker for the PFB molecular subtype of PF-EPNs.

Development and validation of a model for predicting the risk of prostate cancer.

Abnormal hematologic parameters before patients undergoing prostate biopsy play a pivotal role in guiding the surgical management of prostate cancer (PCa) incidence. This study aims to establish the first nomogram for predicting PCa risk for better surgical management. We retrospectively reviewed and analyzed the data including basic information, preoperative hematologic parameters, and imaging examination of 540 consecutive patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy for elevated prostate-specific antigen (PSA) in our medical center between 2017 and 2021. Logistic regression analysis was used to determine the risk factors for PCa occurrence, and the nomogram was constructed to predict PCa occurrence. Finally, the data including 121 consecutive patients in 2022 were prospectively collected to further verify the results. In retrospective analyses, univariate and multivariate logistic analyses identified that three variables including age, diabetes, and De Ritis ratio (aspartate transaminase/alanine transaminase, AST/ALT) were determined to be significantly associated with PCa occurrence. A nomogram was constructed based on these variables for predicting the risk of PCa, and a satisfied predictive accuracy of the model was determined with a C-index of 0.765, supported by a prospective validation group with a C-index of 0.736. The Decision curve analysis showed promising clinical application. In addition, our results also showed that the De Ritis ratio was significantly correlated with the clinical stage of PCa patients, including T, N, and M stages, but insignificantly related to the Gleason score. The increased De Ritis ratio was significantly associated with the risk and clinical stage of PCa and this nomogram with good discrimination could effectively improve individualized surgical management for patient underdoing prostate biopsy.

Heparin-activated procoagulant platelet assay: a flow cytometry-based functional test for heparin-induced thrombocytopenia

BackgroundFunctional platelet activation assays are required for the diagnosis of heparin-induced thrombocytopenia (HIT). Due to their sophisticated methodology, they are only available in reference centers. ObjectivesTo evaluate the diagnostic accuracy of the flow cytometry-based heparin-activated procoagulant platelet (HAPP) assay in the laboratory diagnosis of HIT. MethodsProcoagulant platelets (PCP), defined by the expression of phosphatidylserine and CD62-P, were evaluated by flow cytometry in platelet-rich plasma from healthy donors after incubation with patient sera in the absence and presence of heparin. A sample was considered positive in HAPP assay, if the following 3 criteria were met: 1) the percentage of PCPs was ≥10.3% after incubation with 0.2 IU/mL heparin, 2) the fold increase in presence of 0.2 IU/mL heparin compared with buffer was ≥1.5, and 3) 100 IU/mL of heparin resulted in ≥50% inhibition of PCP. HAPP assay was validated in a prospective cohort (n = 202) of consecutive specimens submitted to our laboratory for serologic diagnosis of HIT. Heparin-induced platelet activation (HIPA) assay was used as the reference standard. ResultsHIT-positive sera induced PCPs in the presence of 0.2 IU/mL heparin, which was inhibited with 100 IU/mL of heparin. In the prospective validation cohort, there were 15 HIPA+ and 187 HIPA- sera. HAPP was positive in 20 samples in this cohort. Using optimized cut-offs, HAPP assay had a sensitivity of 93.3% and specificity of 96.8%. ConclusionHAPP assay is promising as a simple and reliable functional assay for HIT; however, further studies are needed to confirm our results in larger cohorts.

Severe hypernatremia during postoperative care in patients with craniopharyngioma.

We aimed to describe and predict the risk of severe hypernatremia after surgical resection of craniopharyngioma and to identify the association of water intake, urine output, and sodium level change in the patients. The outcome was postoperative severe hypernatremia. We identified risk factors associated with hypernatremia using multivariable regression. We trained machine learning models to predict the outcome. We compared serum sodium change, intravenous input, oral input, total input, urine output, and net fluid balance according to different nurse shifts. Among 234 included patients, 125 developed severe hypernatremia after surgery. The peak incidence occurred during day 0 and day 6 after surgery. The risk was increased in patients with gross total resection (odds ratio (OR) 2.41, P < 0.001), high Puget classification (OR 4.44, P = 0.026), preoperative adrenal insufficiency (OR 2.01, P = 0.040), and preoperative hypernatremia (OR 5.55, P < 0.001). The random forest algorithm had the highest area under the receiver operating characteristic curve (0.770, 95% CI, 0.727-0.813) in predicting the outcome and was validated in the prospective validation cohort. Overnight shifts were associated with the highest serum sodium increase (P = 0.010), less intravenous input (P < 0.001), and less desmopressin use (P < 0.001). The overall incidence of severe hypernatremia after surgical resection of craniopharyngioma was significant, especially in patients with gross total resection, hypothalamus distortion, preoperative adrenal insufficiency, and preoperative severe hypernatremia. Less intravenous input and less desmopressin use were associated with serum sodium increases, especially during overnight shifts.

Upfront Taxane Could Be Superior to Pegylated Liposomal Doxorubicin (PLD): A Retrospective Real-World Analysis of Treatment Sequence Taxane-PLD versus PLD-Taxane in Patients with Metastatic Breast Cancer.

Background: Patients with endocrine-resistant metastatic breast cancer (MBC) require cytostatic therapy. Single-agent taxanes and anthracyclines, including pegylated liposomal doxorubicin (PLD), are standard treatment options. There are no prospective data regarding optimal treatment sequences, and real-world data regarding both treatment options are limited. Methods: We analyzed electronic records of all patients with Her2-negative MBC treated with either first-line PLD or first-line taxane and subsequent crossover at the University Hospital Basel between 2003 and 2021. The primary endpoint was time to next chemotherapy or death (TTNC). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). We used the Kaplan-Meyer method and logrank test to compare time-to-event endpoints and the Fisher exact test to compare discrete variables. Results: We retrospectively identified 42 patients with Her2-negative MBC who have received either single-agent PLD or single-agent taxane as first-line chemotherapy with subsequent crossover, including 23 patients who received first-line PLD and 19 patients who received first-line taxane. Baseline characteristics were similar between treatment groups. Treatment sequence PLD-taxane was significantly inferior to taxane-PLD regarding all endpoints: median TTNC 4.9 vs. 9.9 months (p = 0.006), median OS 17.8 vs. 24.6 months (p = 0.05), median PFS 4.4 vs. 9.0 months (p = 0.005), and ORR 13% vs. 53% (p = 0.01). Conclusions: Here, we report a first retrospective head-to-head comparison of the treatment sequence PLD-taxane versus taxane-PLD in patients with MBC, showing a substantial advantage of using taxanes first, followed by PLD. An inherent treatment bias in favor of first-line taxanes cannot be excluded, thus calling for prospective validation.

Routine perioperative blood tests predict survival of resectable lung cancer

There is growing evidence that inflammatory, immunologic, and metabolic status is associated with cancer patients survival. Here, we built a simple algorithm to predict lung cancer outcome. Perioperative routine blood tests (RBT) of a cohort of patients with resectable primary lung cancer (LC) were analysed. Inflammatory, immunologic, and metabolic profiles were used to create a single algorithm (RBT index) predicting LC survival. A concurrent cohort of patients with resectable lung metastases (LM) was used to validate the RBT index. Charts of 2088 consecutive LC and 1129 LM patients undergoing lung resection were evaluated. Among RBT parameters, C-reactive protein (CRP), lymphocytes, neutrophils, hemoglobin, albumin and glycemia independently correlated with survival, and were used to build the RBT index. Patients with a high RBT index had a higher 5-year mortality than low RBT patients (adjusted HR 1.93, 95% CI 1.62–2.31). High RBT patients also showed a fourfold higher risk of 30-day postoperative mortality (2.3% vs. 0.5%, p 0.0019). The LM analysis validated the results of the LC cohort. We developed a simple and easily available multifunctional tool predicting short-term and long-term survival of curatively resected LC and LM. Prospective external validation of RBT index is warranted.

Multitask Learning with Convolutional Neural Networks and Vision Transformers Can Improve Outcome Prediction for Head and Neck Cancer Patients.

Neural-network-based outcome predictions may enable further treatment personalization of patients with head and neck cancer. The development of neural networks can prove challenging when a limited number of cases is available. Therefore, we investigated whether multitask learning strategies, implemented through the simultaneous optimization of two distinct outcome objectives (multi-outcome) and combined with a tumor segmentation task, can lead to improved performance of convolutional neural networks (CNNs) and vision transformers (ViTs). Model training was conducted on two distinct multicenter datasets for the endpoints loco-regional control (LRC) and progression-free survival (PFS), respectively. The first dataset consisted of pre-treatment computed tomography (CT) imaging for 290 patients and the second dataset contained combined positron emission tomography (PET)/CT data of 224 patients. Discriminative performance was assessed by the concordance index (C-index). Risk stratification was evaluated using log-rank tests. Across both datasets, CNN and ViT model ensembles achieved similar results. Multitask approaches showed favorable performance in most investigations. Multi-outcome CNN models trained with segmentation loss were identified as the optimal strategy across cohorts. On the PET/CT dataset, an ensemble of multi-outcome CNNs trained with segmentation loss achieved the best discrimination (C-index: 0.29, 95% confidence interval (CI): 0.22-0.36) and successfully stratified patients into groups with low and high risk of disease progression (p=0.003). On the CT dataset, ensembles of multi-outcome CNNs and of single-outcome ViTs trained with segmentation loss performed best (C-index: 0.26 and 0.26, CI: 0.18-0.34 and 0.18-0.35, respectively), both with significant risk stratification for LRC in independent validation (p=0.002 and p=0.011). Further validation of the developed multitask-learning models is planned based on a prospective validation study, which has recently completed recruitment.

Validating the early phototherapy prediction tool across cohorts.

Hyperbilirubinemia of the newborn infant is a common disease worldwide. However, recognized early and treated appropriately, it typically remains innocuous. We recently developed an early phototherapy prediction tool (EPPT) by means of machine learning (ML) utilizing just one bilirubin measurement and few clinical variables. The aim of this study is to test applicability and performance of the EPPT on a new patient cohort from a different population. This work is a retrospective study of prospectively recorded neonatal data from infants born in 2018 in an academic hospital, Regensburg, Germany, meeting the following inclusion criteria: born with 34 completed weeks of gestation or more, at least two total serum bilirubin (TSB) measurement prior to phototherapy. First, the original EPPT-an ensemble of a logistic regression and a random forest-was used in its freely accessible version and evaluated in terms of the area under the receiver operating characteristic curve (AUROC). Second, a new version of the EPPT model was re-trained on the data from the new cohort. Third, the predictive performance, variable importance, sensitivity and specificity were analyzed and compared across the original and re-trained models. In total, 1,109 neonates were included with a median (IQR) gestational age of 38.4 (36.6-39.9) and a total of 3,940 bilirubin measurements prior to any phototherapy treatment, which was required in 154 neonates (13.9%). For the phototherapy treatment prediction, the original EPPT achieved a predictive performance of 84.6% AUROC on the new cohort. After re-training the model on a subset of the new dataset, 88.8% AUROC was achieved as evaluated by cross validation. The same five variables as for the original model were found to be most important for the prediction on the new cohort, namely gestational age at birth, birth weight, bilirubin to weight ratio, hours since birth, bilirubin value. The individual risk for treatment requirement in neonatal hyperbilirubinemia is robustly predictable in different patient cohorts with a previously developed ML tool (EPPT) demanding just one TSB value and only four clinical parameters. Further prospective validation studies are needed to develop an effective and safe clinical decision support system.

Prospective validation of the Israeli Score for the prediction of common bile duct stones in patients with acute calculous cholecystitis.

Existing guidelines for predicting common bile duct stones (CBDS) are not specific for acute calculous cholecystitis (ACC). This paper is a posthoc analysis of the S.P.Ri.M.A.C.C study aiming to prospectively validate on a large independent cohort of patients the Israeli Score (IS) in predicting CBDS in patients with ACC. The S.P.Ri.M.A.C.C. study is an observational multicenter prospective study endorsed by the World Society of Emergency Surgery (WSES). Between September 1st, 2021, and September 1st, 2022, 1201 participants were included. The Chi-Square test was used to compare categorical data. A Cochran-Armitage test was run to determine whether a linear trend existed between the IS and the presence of CBDS. To assess the accuracy of the prediction model, the receiver operating characteristic (ROC) curve was generated, and the area under the ROC curve (AUC) was calculated. Logistic regression was run to obtain Odds Ratio (OR). A two-tailed p < 0.05 was considered statistically significant. The rate of CBDS was 1.8% in patients with an IS of 0, 4.2% in patients with an IS of 1, 24.5% in patients with 2 and 56.3% in patients with 3 (p < 0.001). The Cochran-Armitage test of trend showed a statistically significant linear trend, p < 0.001. Patients with an IS of 3 had 64.4 times (95% CI 24.8-166.9) higher odds of having associated CBDS than patients with an IS of 0. The AUC of the ROC curve of IS for the prediction of CBDS was 0.809 (95% CI 0.752-0.865, p < 0.001). By applying the highest cut-off point (3), the specificity reached 99%, while using the lowest cut-off value (0), the sensitivity reached 100%. The IS is a reliable tool to predict CBDS associated with ACC. The algorithm derived from the IS could optimize the management of patients with ACC.

Infections after chimeric antigen receptor (CAR)-T-cell therapy for hematologic malignancies.

Chimeric antigen receptor (CAR)-T-cell therapies have revolutionized the management of acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma but come at the price of unique toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and long-term "on-target off-tumor" effects. All of these factors increase infection risk in an already highly immunocompromised patient population. Indeed, infectious complications represent the key determinant of non-relapse mortality after CAR-T cells. The temporal distribution of these risk factors shapes different infection patterns early versus late post-CAR-T-cell infusion. Furthermore, due to the expression of their targets on B lineage cells at different stages of differentiation, CD19, and B-cell maturation antigen (BCMA) CAR-T cells induce distinct immune deficits that could require different prevention strategies. Infection incidence is the highest during the first month post-infusion and subsequently decreases thereafter. However, infections remain relatively common even a year after infusion. Bacterial infections predominate early after CD19, while a more equal distribution between bacterial and viral causes is seen after BCMA CAR-T-cell therapy, and fungal infections are universally rare. Cytomegalovirus (CMV) and other herpesviruses are increasingly breported, but whether routine monitoring is warranted for all, or a subgroup of patients, remains to be determined. Clinical practices vary substantially between centers, and many areas of uncertainty remain, including CMV monitoring, antibacterial and antifungal prophylaxis and duration, use of immunoglobulin replacement therapy, and timing of vaccination. Risk stratification tools are available and may help distinguish between infectious and non-infectious causes of fever post-infusion and predict severe infections. These tools need prospective validation, and their integration in clinical practice needs to be systematically studied.

Prospective validation of an equation based on plasma cystatin C for monitoring the glomerular filtration rate in children treated with cisplatin or ifosfamide for cancer.

We recently proposed an equation to estimate the glomerular filtration rate (GFR) in children with cancer based on plasma cystatin C and serum creatinine levels together with body weight (the "CysPed equation"). The current clinical study reports a prospective evaluation of this equation in 18 children treated by nephrotoxic chemotherapy. The CysPed equation resulted in less bias and greater precision compared to two equations previously proposed equations by Schwartz, with or without plasma cystatin C. Moreover, the decrease in GFR due to chemotherapy was clearly identified by the CysPed equation. This equation may be used to monitor the renal function in childhood cancer units.

Reimagining the Value of Brachial-Ankle Pulse Wave Velocity as a Biomarker of Cardiovascular Disease Risk-A Call to Action on Behalf of VascAgeNet.

This review critiques the literature supporting clinical assessment and management of cardiovascular disease and cardiovascular disease risk stratification with brachial-ankle pulse wave velocity (baPWV). First, we outline what baPWV actually measures-arterial stiffness of both large central elastic arteries and medium-sized muscular peripheral arteries of the lower limb. Second, we argue that baPWV is not a surrogate for carotid-femoral pulse wave velocity. While both measures are dependent on the properties of the aorta, baPWV is also strongly dependent on the muscular arteries of the lower extremities. Increased lower-extremity arterial stiffness amplifies and hastens wave reflections at the level of the aorta, widens pulse pressure, increases afterload, and reduces coronary perfusion. Third, we used an established evaluation framework to identify the value of baPWV as an independent vascular biomarker. There is sufficient evidence to support (1) proof of concept; (2) prospective validation; (3) incremental value; and (4) clinical utility. However, there is limited or no evidence to support (5) clinical outcomes; (6) cost-effectiveness; (8) methodological consensus; or (9) reference values. Fourth, we address future research requirements. The majority of the evaluation criteria, (1) proof of concept, (2) prospective validation, (3) incremental value, (4) clinical utility and (9) reference values, can be supported using existing cohort datasets, whereas the (5) clinical outcomes and (6) cost-effectiveness criteria require prospective investigation. The (8) methodological consensus criteria will require an expert consensus statement. Finally, we finish this review by providing an example of a future clinical practice model.

Prospective Multicenter Validation of the Stockholm3 Test in a Central European Cohort

BackgroundIt has been shown that the Stockholm3 test decreases overdetection of prostate cancer (PCa) while retaining the ability to detect clinically significant PCa (csPCa) in a Swedish population. However, the test includes potentially population-specific testing of single-nucleotide polymorphisms and has yet not been validated outside Scandinavia. ObjectiveTo assess the performance of the Stockholm3 test in discriminating csPCa in a Central European cohort undergoing prostate biopsy (PBx). Design, setting, and participantsThis prospective multicenter validation study was conducted from August 2020 to September 2022 at two centers in Switzerland and one center in Germany. The study involved 342 men undiagnosed with PCa who were scheduled for PBx after prostate-specific antigen (PSA) testing and subsequent magnetic resonance imaging (MRI) of the prostate. Before PBx, participants had a blood sample taken for Stockholm3 testing. Outcome measurements and statistical analysisThe primary outcome was the accuracy of the Stockholm3 test in detecting csPCa (International Society of Urological Pathology grade group [GG] ≥2) according to the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, and the clinical consequences of using the model. Results and limitationsThe Stockholm3 test with a cutoff of 11% for csPCa detection had sensitivity of 92.3% (95% confidence interval [CI] 86.9–95.9%), specificity of 32.6% (95% CI 26.0–39.8%), a positive predictive value of 53.2% (95% CI 47.0–59.2%), and a negative predictive value of 83.6% (95% CI 73–91.2%). It showed superior discrimination for csPCa (AUC 0.77, 95% CI 0.72–0.82) in comparison to PSA (AUC 0.66, 95% CI 0.61–0.72; p < 0.001). Using a Stockholm3 cutoff of 11%, PBx could have been omitted for 73 men (21.0%), and 12/154 (8%) csPCa and 2/72 (2.8%) GG >2 cases would have been missed. Limitations include population selection bias. ConclusionsOur results show favorable clinical outcomes for the blood-based Stockholm3 biomarker test in a Central European patient cohort. Patient summaryThe Stockholm3 blood test shows better accuracy in predicting prostate cancer than the more common PSA (prostate-specific antigen) test.

LBA100 CUP-ONE trial: A prospective double-blind validation of molecular classifiers in the diagnosis of cancer of unknown primary and clinical outcomes

LBA100 CUP-ONE trial: A prospective double-blind validation of molecular classifiers in the diagnosis of cancer of unknown primary and clinical outcomes

Prospective Validation of Single Nucleotide Polymorphisms as Predictors of Gastrointestinal, Genitourinary, and Sexual Patient-Reported Outcomes Following Radiotherapy for Prostate Cancer.

Radiotherapy (RT) for localized prostate cancer (PC) can adversely impact gastrointestinal (GI), genitourinary (GU), and sexual quality of life (QoL). Biomarkers are needed to accurately predict individualized risk of toxicity and enable tailoring of therapy. Single nucleotide polymorphisms (SNPs) have been reported as potential predictors of RT-related toxicities, but have not been associated with patient-report outcomes (PRO) in prospective cohorts. In this study, we sought to validate these SNPs in a prospective registry study of RT for PC, with high-quality prospectively collected PRO data. Men with low/intermediate risk PC were consented to a multicenter companion registry study associated with the PARTIQoL Phase III Randomized Trial of proton vs. photon RT. Patients received RT to prostate/seminal vesicles per protocol. Androgen deprivation therapy and pelvic lymph node RT were not allowed. 95 patients enrolled between 2014-2020 at a single institution had blood specimens available for germline DNA analysis. 172 SNPs previously reported to correlate with GI, GU, and/or sexual RT toxicities were genotyped. PRO data through the Expanded Prostate Cancer Index Composite (EPIC) were collected prior to RT and at prespecified follow-up (FU) time points. Change of the EPIC score from baseline was compared between genotypes of previously identified SNPs using a two-sample t-test. Significant clinically meaningful QoL differences were identified by an effect size of at least 0.4σ with two-sided p<0.05, where σ represents the standard deviation of the score change. Median FU was 39 months (r, 6-89). Median age was 68 years (r, 52-83). Features at diagnosis include: 77% T1c, median PSA 5.8 (r, 1.43-15.1), 53% Gleason 7, median prostate volume 45.5cc (r, 16-142). 43% received proton RT; 53% had a rectal spacer. 40% received 79.2 Gy/44 fractions; 60% received 70 Gy/28 fractions. Between 6 to 24 months post-RT, there were 19 SNPs that were significantly associated with clinically meaningful decreases in GI QoL scores, 19 that were significantly associated with clinically meaningful decreases in GU QoL scores, and 10 SNPs that were significantly associated with clinically meaningful decreases in sexual QoL scores. Three BRCA2 SNPs (rs1801439, rs1801499, rs1799944) were significantly associated with clinically meaningful decreases in both GI and GU QoL scores. Of the 172 SNPs previously reported to be associated with GI, GU, and/or sexual toxicity after prostate RT, 23% were validated for domain-specific QoL detriment. Ongoing analyses include integrated modeling of dosimetry and SNP data for prediction of toxicities and PRO, and evaluation of potential interactions between RT modality (proton/photon) and QoL-associated SNPs.

EP26.04: Prospective validation of a clinical prediction model for diagnosing adenomyosis with ultrasound

EP26.04: Prospective validation of a clinical prediction model for diagnosing adenomyosis with ultrasound

EP06.14: Prenatal assessment of tentorium cerebelli by a Doppler technology with highly sensitive flow: a prospective validation study

EP06.14: Prenatal assessment of tentorium cerebelli by a Doppler technology with highly sensitive flow: a prospective validation study