Correction: Cost-effectiveness of talazoparib for patients with locally advanced or metastasized breast cancer in Germany.

[This corrects the article DOI: 10.1371/journal.pone.0278460.].

Assessment of epicardial adipose tissue on virtual non-contrast images derived from photon-counting detector coronary CTA datasets.

OBJECTIVES: To assess epicardial adipose tissue (EAT) volume and attenuation of different virtual non-contrast (VNC) reconstructions derived from coronary CTA (CCTA) datasets of a photon-counting detector (PCD) CT-system to replace true non-contrast (TNC) series. METHODS: Consecutive patients (n = 42) with clinically indicated CCTA and coronary TNC were included. Two VNC series were reconstructed, using a conventional (VNCConv) and a novel calcium-preserving (VNCPC) algorithm. EAT was segmented on TNC, VNCConv, VNCPC, and CCTA (CTA-30) series using thresholds of -190 to -30 HU and an additional segmentation on the CCTA series with an upper threshold of 0 HU (CTA0). EAT volumes and their histograms were assessed for each series. Linear regression was used to correlate EAT volumes and the Euclidian distance for histograms. The paired t-test and the Wilcoxon signed-rank test were used to assess differences for parametric and non-parametric data. RESULTS: EAT volumes from VNC and CCTA series showed significant differences compared to TNC (all p < .05), but excellent correlation (all R2 > 0.9). Measurements on the novel VNCPC series showed the best correlation (R2 = 0.99) and only minor absolute differences compared to TNC values. Mean volume differences were -12%, -3%, -13%, and +10% for VNCConv, VNCPC, CTA-30, and CTA0 compared to TNC. Distribution of CT values on VNCPC showed less difference to TNC than on VNCConv (mean attenuation difference +7% vs. +2%; Euclidean distance of histograms 0.029 vs. 0.016). CONCLUSIONS: VNCPC-reconstructions of PCD-CCTA datasets can be used to reliably assess EAT volume with a high accuracy and only minor differences in CT values compared to TNC. Substitution of TNC would significantly decrease patient's radiation dose. KEY POINTS: • Measurement of epicardial adipose tissue (EAT) volume and attenuation are feasible on virtual non-contrast (VNC) series with excellent correlation to true non-contrast series (all R2>0.9). • Differences in VNC algorithms have a significant impact on EAT volume and CT attenuation values. • A novel VNC algorithm (VNCPC) enables reliable assessment of EAT volume and attenuation with superior accuracy compared to measurements on conventional VNC- and CCTA-series.

Cost-effectiveness of talazoparib for patients with locally advanced or metastasized breast cancer in Germany.

This study evaluated factors that influence the cost-effectiveness of talazoparib, particularly for patients with a germline breast-cancer-gene-(brca)-mutation and locally advanced or metastasized breast cancer within the context of the German healthcare system. We constructed a partitioned survival model to compare medical costs and treatment effectiveness for patients with such cancers over 45 months. Transition probabilities were derived from survival data from a randomized Phase-III EMBRACA trial, utilities based on published reports, and costs in Euros, which included costs for drug acquisition, clinical monitoring, and treatment of adverse events. Willingness-to-pay thresholds were set to be multiples of the current German per capita gross domestic product. Treatment with talazoparib led to a gain of 0.32 life-years (0.22 quality-adjusted life-years). The mean total cost of €84,003 for talazoparib and €12,741 for standard therapy resulted in an incremental cost-effectiveness ratio of €223,246 per life-year and €323,932 per quality-adjusted life-year gained, indicating that talazoparib is unlikely to be cost-effective at current pricing.

Assessment of quantitative information for radiation therapy at a first-generation clinical photon-counting computed tomography scanner.

As one of the latest developments in X-ray computed tomography (CT), photon-counting technology allows spectral detection, demonstrating considerable advantages as compared to conventional CT. In this study, we investigated the use of a first-generation clinical photon-counting computed tomography (PCCT) scanner and estimated proton relative (to water) stopping power (RSP) of tissue-equivalent materials from virtual monoenergetic reconstructions provided by the scanner. A set of calibration and evaluation tissue-equivalent inserts were scanned at 120 kVp. Maps of relative electron density (RED) and effective atomic number (EAN) were estimated from the reconstructed virtual monoenergetic images (VMI) using an approach previously applied to a spectral CT scanner with dual-layer detector technology, which allows direct calculation of RSP using the Bethe-Bloch formula. The accuracy of RED, EAN, and RSP was evaluated by root-mean-square errors (RMSE) averaged over the phantom inserts. The reference RSP values were obtained experimentally using a water column in an ion beam. For RED and EAN, the reference values were calculated based on the mass density and the chemical composition of the inserts. Different combinations of low- and high-energy VMIs were investigated in this study, ranging from 40 to 190 keV. The overall lowest error was achieved using VMIs at 60 and 180 keV, with an RSP accuracy of 1.27% and 0.71% for the calibration and the evaluation phantom, respectively.

Application of single- and dual-energy CT brain tissue segmentation to PET monitoring of proton therapy.

The purpose of this work was to evaluate the ability of single and dual energy computed tomography (SECT, DECT) to estimate tissue composition and density for usage in Monte Carlo (MC) simulations of irradiation induced ß + activity distributions. This was done to assess the impact on positron emission tomography (PET) range verification in proton therapy. A DECT-based brain tissue segmentation method was developed for white matter (WM), grey matter (GM) and cerebrospinal fluid (CSF). The elemental composition of reference tissues was assigned to closest CT numbers in DECT space (DECTdist). The method was also applied to SECT data (SECTdist). In a validation experiment, the proton irradiation induced PET activity of three brain equivalent solutions (BES) was compared to simulations based on different tissue segmentations. Five patients scanned with a dual source DECT scanner were analyzed to compare the different segmentation methods. A single magnetic resonance (MR) scan was used for comparison with an established segmentation toolkit. Additionally, one patient with SECT and post-treatment PET scans was investigated. For BES, DECTdist and SECTdist reduced differences to the reference simulation by up to 62% when compared to the conventional stoichiometric segmentation (SECTSchneider). In comparison to MR brain segmentation, Dice similarity coefficients for WM, GM and CSF were 0.61, 0.67 and 0.66 for DECTdist and 0.54, 0.41 and 0.66 for SECTdist. MC simulations of PET treatment verification in patients showed important differences between DECTdist/SECTdist and SECTSchneider for patients with large CSF areas within the treatment field but not in WM and GM. Differences could be misinterpreted as PET derived range shifts of up to 4 mm. DECTdist and SECTdist yielded comparable activity distributions, and comparison of SECTdist to a measured patient PET scan showed improved agreement when compared to SECTSchneider. The agreement between predicted and measured PET activity distributions was improved by employing a brain specific segmentation applicable to both DECT and SECT data.

Effectiveness of automated quantification of pulmonary perfused blood volume using dual-energy CTPA for the severity assessment of acute pulmonary embolism.

PURPOSE: The purpose of this study was to determine whether automated quantification of pulmonary perfused blood volume (PBV) in dual-energy computed tomography pulmonary angiography is of diagnostic value in assessing the severity of acute pulmonary embolism (PE). MATERIALS AND METHODS: Ethical approval and informed consent were waived by the responsible institutional review board for this retrospective study. Of 224 consecutive patients with dual-energy computed tomography pulmonary angiographic findings positive for acute PE, we excluded 153 patients because of thoracic comorbidities (n = 130), missing data (n = 11), severe artifacts (n = 11), or inadequate enhancement (n = 1). Automated quantification of PBV was performed in the remaining 71 patients (mean [SD] age, 62 [16] years) with acute PE and no cardiopulmonary comorbidities. Perfused blood volume values adjusted for age and sex were correlated with the Qanadli obstruction score, morphological computed tomographic signs of right heart dysfunction, serum levels of troponin, and the necessity for intensive care unit (ICU) admission. RESULTS: Dual-energy computed tomography pulmonary angiography-derived PBV values inversely correlated with the Qanadli score (r = -0.46; P < 0.001), the right and left ventricle (RV/LV) ratio (r = -0.52; P < 0.001), and troponin I (r = -0.45; P = 0.001). The patients with global PBV values lower than 60% were significantly more likely to require admission to an ICU than did the patients with global pulmonary PBV of 60% or higher (47% vs 11%; P = 0.003; positive predictive value, 47%; negative predictive value, 89%). On the univariate analysis, a significant negative correlation was found between the global PBV values and the Qanadli obstruction score (r = -0.46; P < 0.001), the RV/LV diameter ratio (r = -0.52; P < 0.001), and the necessity for ICU admission (r = -0.39; P = 0.001). On the retrospective multivariate regression analysis, the areas under the receiver operating characteristic curve for the prediction of ICU admission were 0.75 for the pulmonary PBV, 0.83 for the Qanadli obstruction score, 0.68 for the computed tomographic signs of right heart dysfunction (interventricular septal bowing and/or contrast reflux), and 0.76 for the RV/LV diameter ratio. CONCLUSIONS: Dual-energy computed tomography pulmonary angiography can be used for an immediate, reader-independent estimation of global pulmonary PBV in acute PE, which inversely correlates with thrombus load, laboratory parameters of PE severity, and the necessity for ICU admission.

High-resolution cine MRI with TGRAPPA for fast assessment of left ventricular function at 3 Tesla.

PURPOSE: To implement and evaluate the accuracy of multislice dual-breath hold cine MR for analysis of global systolic and diastolic left ventricular function at 3T. MATERIALS AND METHODS: 25 patients referred to cardiac MR underwent cine imaging at 3T (MAGNETOM Verio) using prospective triggered SSFP (TR 3.1 ms; TE 1.4 ms; FA 60°). Analysis of LV function was performed using a standard non-accelerated single-slice approach (STD) with multiple breath-holds and an accelerated multi-slice technique (TGRAPPA; R=4) encompassing the ventricles with 5 slices/breath-hold. Parameters of spatial and temporal resolution were kept identical (pixel: 1.9 × 2.5 mm(2); temporal resolution: 47 ms). Data of both acquisition techniques were analyzed by two readers using semiautomatic algorithms (syngoARGUS) with respect to EDV, ESV, EF, myocardial mass (MM), peak filling rate (PFR) and peak ejection rate (PER) including assessment of interobserver agreement. RESULTS: Volumetric results of the TGRAPPA approach did not show significant differences to the STD approach for left ventricular ejection fraction (62.3 ± 10.6 vs. 61.0 ± 8.4, P=0.2), end-diastolic volume (135.8 ± 47.5 vs. 130.8 ± 46.4, P=0.07), endsystolic volume (53.0 ± 29.7 vs. 53.1 ± 32.7, P=0.99) and myocardial mass (114.2 ± 32.5 vs. 114.6±30.6, P=0.9). Moreover, a comparison of peak ejection rate (601.3 ± 190.2 vs. 590.8 ± 218.2, P=0.8) and peak filling rate (535.1±191.2 vs. 535.4 ± 210.7, P=0.99) did not reveal significant differences between the two groups. Limits in interobserver agreement were low for all systolic and diastolic parameters in both groups (P ≥ 0.05). Total acquisition time for STD was 273 ± 124 s and 34 ± 5 s for TGRAPPA (P ≤ 0.001). Evaluation time for standard and multislice approach was equal (10.8 ± 1.4 vs. 9.8 ± 2.1 min; P=0.08).

Comparison of dual-energy computed tomography of the heart with single photon emission computed tomography for assessment of coronary artery stenosis and of the myocardial blood supply.

To evaluate the performance of dual-energy computed tomography (CT) for integrative imaging of the coronary artery morphology and the myocardial blood supply, 36 patients (15 women, mean age 57 +/- 11 years) with equivocal or incongruous single photon emission CT (SPECT) results were investigated by a single-contrast medium-enhanced, retrospectively electrocardiographic-gated dual-energy CT (DECT) scan with simultaneous acquisition of high and low x-ray spectra. Thirteen patients subsequently underwent invasive coronary angiography (ICA). The DECT data were used to reconstruct anatomic coronary CT angiographic images and to map the myocardial iodine distribution within the left ventricular myocardium. Two independent observers analyzed all DECT studies for stenosis and myocardial iodine defects. A segmental comparison was performed between the stress/rest SPECT perfusion defects and DECT iodine defects and between the ICA and coronary CT angiographic findings for stenosis. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were estimated, along with the kappa statistics. Overall, DECT had 92% sensitivity and 93% specificity, with 93% accuracy for detecting any type of myocardial perfusion defect seen on SPECT. Contrast defects at DECT correctly identified 85 (96%) of 89 fixed and 60 (88%) of 68 reversible myocardial perfusion defects. The interobserver agreement was very good (weighted kappa = 0.87). Compared with ICA, coronary CT angiography had 90% sensitivity, 94% specificity, and 93% accuracy for the detection of >50% stenosis. In conclusion, our initial experience suggests that DECT, as a single examination, might be promising for the integrative analysis of the coronary artery morphology and the myocardial blood supply and is in good agreement with ICA and SPECT.