Regional Histopathology and Prostate MRI Positivity: A Secondary Analysis of the PROMIS Trial.

Background The effects of regional histopathologic changes on prostate MRI scans have not been accurately quantified in men with an elevated prostate-specific antigen (PSA) level and no previous biopsy. Purpose To assess how Gleason grade, maximum cancer core length (MCCL), inflammation, prostatic intraepithelial neoplasia (PIN), or atypical small acinar proliferation within a Barzell zone affects the odds of MRI visibility. Materials and Methods In this secondary analysis of the Prostate MRI Imaging Study (PROMIS; May 2012 to November 2015), consecutive participants who underwent multiparametric MRI followed by a combined biopsy, including 5-mm transperineal mapping (TPM), were evaluated. TPM pathologic findings were reported at the whole-prostate level and for each of 20 Barzell zones per prostate. An expert panel blinded to the pathologic findings reviewed MRI scans and declared which Barzell areas spanned Likert score 3-5 lesions. The relationship of Gleason grade and MCCL to zonal MRI outcome (visible vs nonvisible) was assessed using generalized linear mixed-effects models with random intercepts for individual participants. Inflammation, PIN, and atypical small acinar proliferation were similarly assessed in men who had negative TPM results. Results Overall, 161 men (median age, 62 years [IQR, 11 years]) were evaluated and 3179 Barzell zones were assigned MRI status. Compared with benign areas, the odds of MRI visibility were higher when a zone contained cancer with a Gleason score of 3+4 (odds ratio [OR], 3.1; 95% CI: 1.9, 4.9; P < .001) or Gleason score greater than or equal to 4+3 (OR, 8.7; 95% CI: 4.5, 17.0; P < .001). MCCL also determined visibility (OR, 1.24 per millimeter increase; 95% CI: 1.15, 1.33; P < .001), but odds were lower with each prostate volume doubling (OR, 0.7; 95% CI: 0.5, 0.9). In men who were TPM-negative, the presence of PIN increased the odds of zonal visibility (OR, 3.7; 95% CI: 1.5, 9.1; P = .004). Conclusion An incremental relationship between cancer burden and prostate MRI visibility was observed. Prostatic intraepithelial neoplasia contributed to false-positive MRI findings. ClinicalTrials.gov registration no. NCT01292291 © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Harmath in this issue.

Tailored Bayes: a risk modeling framework under unequal misclassification costs.

Risk prediction models are a crucial tool in healthcare. Risk prediction models with a binary outcome (i.e., binary classification models) are often constructed using methodology which assumes the costs of different classification errors are equal. In many healthcare applications, this assumption is not valid, and the differences between misclassification costs can be quite large. For instance, in a diagnostic setting, the cost of misdiagnosing a person with a life-threatening disease as healthy may be larger than the cost of misdiagnosing a healthy person as a patient. In this article, we present Tailored Bayes (TB), a novel Bayesian inference framework which "tailors" model fitting to optimize predictive performance with respect to unbalanced misclassification costs. We use simulation studies to showcase when TB is expected to outperform standard Bayesian methods in the context of logistic regression. We then apply TB to three real-world applications, a cardiac surgery, a breast cancer prognostication task, and a breast cancer tumor classification task and demonstrate the improvement in predictive performance over standard methods.

False Positive Multiparametric Magnetic Resonance Imaging Phenotypes in the Biopsy-naïve Prostate: Are They Distinct from Significant Cancer-associated Lesions? Lessons from PROMIS.

BACKGROUND: False positive multiparametric magnetic resonance imaging (mpMRI) phenotypes prompt unnecessary biopsies. The Prostate MRI Imaging Study (PROMIS) provides a unique opportunity to explore such phenotypes in biopsy-naïve men with raised prostate-specific antigen (PSA) and suspected cancer. OBJECTIVE: To compare mpMRI lesions in men with/without significant cancer on transperineal mapping biopsy (TPM). DESIGN, SETTING, AND PARTICIPANTS: PROMIS participants (n=235) underwent mpMRI followed by a combined biopsy procedure at University College London Hospital, including 5-mm TPM as the reference standard. Patients were divided into four mutually exclusive groups according to TPM findings: (1) no cancer, (2) insignificant cancer, (3) definition 2 significant cancer (Gleason ≥3+4 of any length and/or maximum cancer core length ≥4mm of any grade), and (4) definition 1 significant cancer (Gleason ≥4+3 of any length and/or maximum cancer core length ≥6mm of any grade). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Index and/or additional lesions present in 178 participants were compared between TPM groups in terms of number, conspicuity, volume, location, and radiological characteristics. RESULTS AND LIMITATIONS: Most lesions were located in the peripheral zone. More men with significant cancer had two or more lesions than those without significant disease (67% vs 37%; p< 0.001). In the former group, index lesions were larger (mean volume 0.68 vs 0.50 ml; p< 0.001, Wilcoxon test), more conspicuous (Likert 4-5: 79% vs 22%; p< 0.001), and diffusion restricted (mean apparent diffusion coefficient [ADC]: 0.73 vs 0.86; p< 0.001, Wilcoxon test). In men with Likert 3 index lesions, log2PSA density and index lesion ADC were significant predictors of definition 1/2 disease in a logistic regression model (mean cross-validated area under the receiver-operator characteristic curve: 0.77 [95% confidence interval: 0.67-0.87]). CONCLUSIONS: Significant cancer-associated MRI lesions in biopsy-naïve men have clinical-radiological differences, with lesions seen in prostates without significant disease. MRI-calculated PSA density and ADC could predict significant cancer in those with indeterminate MRI phenotypes. PATIENT SUMMARY: Magnetic resonance imaging (MRI) lesions that mimic prostate cancer but are, in fact, benign prompt unnecessary biopsies in thousands of men with raised prostate-specific antigen. In this study we found that, on closer look, such false positive lesions have different features from cancerous ones. This means that doctors could potentially develop better tools to identify cancer on MRI and spare some patients from unnecessary biopsies.

Development and External Validation of Prediction Models for 10-Year Survival of Invasive Breast Cancer. Comparison with PREDICT and CancerMath.

Purpose: To compare PREDICT and CancerMath, two widely used prognostic models for invasive breast cancer, taking into account their clinical utility. Furthermore, it is unclear whether these models could be improved.Experimental Design: A dataset of 5,729 women was used for model development. A Bayesian variable selection algorithm was implemented to stochastically search for important interaction terms among the predictors. The derived models were then compared in three independent datasets (n = 5,534). We examined calibration, discrimination, and performed decision curve analysis.Results: CancerMath demonstrated worse calibration performance compared with PREDICT in estrogen receptor (ER)-positive and ER-negative tumors. The decline in discrimination performance was -4.27% (-6.39 to -2.03) and -3.21% (-5.9 to -0.48) for ER-positive and ER-negative tumors, respectively. Our new models matched the performance of PREDICT in terms of calibration and discrimination, but offered no improvement. Decision curve analysis showed predictions for all models were clinically useful for treatment decisions made at risk thresholds between 5% and 55% for ER-positive tumors and at thresholds of 15% to 60% for ER-negative tumors. Within these threshold ranges, CancerMath provided the lowest clinical utility among all the models.Conclusions: Survival probabilities from PREDICT offer both improved accuracy and discrimination over CancerMath. Using PREDICT to make treatment decisions offers greater clinical utility than CancerMath over a range of risk thresholds. Our new models performed as well as PREDICT, but no better, suggesting that, in this setting, including further interaction terms offers no predictive benefit. Clin Cancer Res; 24(9); 2110-5. ©2018 AACR.

Ventilatory limitation and dynamic hyperinflation during exercise testing in Cystic Fibrosis.

OBJECTIVE: To investigate the presence of dynamic hyperinflation after the Modified Shuttle Test (MST) and its relationship with lung function, exercise tolerance, and clinical symptoms in Cystic Fibrosis (CF). METHODS: Retrospective observational study. Subjects in clinically stable condition with a CF diagnosis based on a positive sweat test (chloride >60 mEq/L) and/or presence of two disease causing mutations, with available data on MST, spirometry, maximal voluntary ventilation, and inspiratory capacity manoeuvres were considered for the analysis. Breathing reserve was calculated and a threshold value of 0.7 was subsequently chosen as a value of pulmonary mechanical limit. Subjects were then categorized into two groups according to the change in the inspiratory capacity from rest to peak exercise. Unconditional logistic regression was used to estimate unadjusted odds ratios, 95% confidence intervals and P-values. RESULTS: Twenty-two subjects demonstrated evidence of dynamic hyperinflation during the MST. Thirteen out of 22 subjects were ventilatory limited during exercise including 5 of those without evidence of dynamic hyperinflation (P = 0.24). No combination of variables resulted in a parsimonious regression model. CONCLUSIONS: Dynamic hyperinflation is common in CF and it is not associated with traditionally defined ventilatory limitation parameters during the MST. Pediatr Pulmonol. 2017;52:29-33. © 2016 Wiley Periodicals, Inc.

Isocapnic hyperpnea with a portable device in Cystic Fibrosis: an agreement study between two different set-up modalities.

To evaluate the bias and precision of the respiratory muscle training device formulas to predict respiratory minute volume (RMV) and volume of the reservoir bag (BV) on a cohort of subjects with Cystic Fibrosis (CF). CF patients with available pulmonary function tests and maximal voluntary manoeuvres were included in the study. Vital capacity and maximal voluntary ventilation were extracted from subjects' records and then inserted to the manufacturer's formulas to obtain RMV and BV (measured setting). RMV and BV were compared according to standard and measured formulas in males and females. Sample was described and then processed using Bland-Altman analysis. Bland-Altman analysis for RMV revealed a bias and precision of 8.8 ± 29 L/min in males and 28.8 ± 16 L/min in females; 0.4 ± 0.5 L in males and 0.7 ± 0.4 L in females for BV. Concordance correlation coefficients for RMV were -0.03 in males and 0.02 in females; 0.22 in males and 0.03 in females for BV, reinforcing an unsatisfactory concordance between measured and manufacturer setting. This study shows considerable discrepancies between the two methods, making the degree of agreement not clinically acceptable. This might cause inappropriate setting and disservice to patients with CF.