RECIST 1.1 Target Lesion Categorical Response in Metastatic Renal Cell Carcinoma: A Comparison of Conventional versus Volumetric Assessment.

Purpose To investigate Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) approximations of target lesion tumor burden by comparing categorical treatment response according to conventional RECIST versus actual tumor volume measurements of RECIST target lesions. Materials and Methods This is a retrospective cohort study of individuals with metastatic renal cell carcinoma enrolled in a clinical trial (from 2003 to 2017) and includes individuals who underwent baseline and at least one follow-up chest, abdominal, and pelvic CT study and with at least one target lesion. Target lesion volume was assessed by (a) Vmodel, a spherical model of conventional RECIST 1.1, which was extrapolated from RECIST diameter, and (b) Vactual, manually contoured volume. Volumetric responses were determined by the sum of target lesion volumes (Vmodel-sum TL and Vactual-sum TL, respectively). Categorical volumetric thresholds were extrapolated from RECIST. McNemar tests were used to compare categorical volume responses. Results Target lesions were assessed at baseline (638 participants), week 9 (593 participants), and week 17 (508 participants). Vmodel-sum TL classified more participants as having progressive disease (PD), compared with Vactual-sum TL at week 9 (52 vs 31 participants) and week 17 (57 vs 39 participants), with significant overall response discordance (P < .001). At week 9, 25 (48%) of 52 participants labeled with PD by Vmodel-sum TL were classified as having stable disease by Vactual-sum TL. Conclusion A model of RECIST 1.1 based on a single diameter measurement more frequently classified PD compared with response assessment by actual measured tumor volume. Keywords: Urinary, Kidney, Metastases, Oncology, Tumor Response, Volume Analysis, Outcomes Analysis ClinicalTrials.gov registration no. NCT01865747 © RSNA, 2023 Supplemental material is available for this article.

A comparison of breast and lung doses from chest CT scans using organ-based tube current modulation (OBTCM) vs. Automatic tube current modulation (ATCM).

PURPOSE: The purpose of this work was to estimate and compare breast and lung doses of chest CT scans using organ-based tube current modulation (OBTCM) to those from conventional, attenuation-based automatic tube current modulation (ATCM) across a range of patient sizes. METHODS: Thirty-four patients (17 females, 17 males) who underwent clinically indicated CT chest/abdomen/pelvis (CAP) examinations employing OBTCM were collected from two multi-detector row CT scanners. Patient size metric was assessed as water equivalent diameter (Dw ) taken at the center of the scan volume. Breast and lung tissues were segmented from patient image data to create voxelized models for use in a Monte Carlo transport code. The OBTCM schemes for the chest portion were extracted from the raw projection data. ATCM schemes were estimated using a recently developed method. Breast and lung doses for each TCM scenario were estimated for each patient model. CTDIvol -normalized breast (nDbreast ) and lung (nDlung ) doses were subsequently calculated. The differences between OBTCM and ATCM normalized organ dose estimates were tested using linear regression models that included CT scanner and Dw as covariates. RESULTS: Mean dose reduction from OBTCM in nDbreast was significant after adjusting for the scanner models and patient size (P = 0.047). When pooled with females and male patient, mean dose reduction from OBTCM in nDlung was observed to be trending after adjusting for the scanner model and patient size (P = 0.085). CONCLUSIONS: One specific manufacturer's OBTCM was analyzed. OBTCM was observed to significantly decrease normalized breast relative to a modeled version of that same manufacturer's ATCM scheme. However, significant dose savings were not observed in lung dose over all. Results from this study support the use of OBTCM chest protocols for females only.

Spreading the sharing economy: Institutional conditions for the international diffusion of Uber, 2010-2017.

This study examines the factors that facilitated the international diffusion of Uber, one of the fastest growing global companies in the sharing economy. We particularly focus on the legal and institutional conditions under which this ride-sharing platform could spread to customers online. Using a unique cross-national, longitudinal dataset, we employ event history models to investigate the effect of institutional environment on the diffusion of Uber. The results suggest that the establishment of the rule of law has a positive impact on the spread of Uber, even after controlling for economic and political characteristics. In addition, the overall quality of governmental regulations on markets is positively related to the diffusion of this ride-sharing platform. Our study contributes to the emerging literature on the sharing economy by identifying critical institutional factors that enable the transformation of business models worldwide.

Patient and site characteristics associated with pirfenidone and nintedanib use in the United States; an analysis of idiopathic pulmonary fibrosis patients enrolled in the Pulmonary Fibrosis Foundation Patient Registry.

BACKGROUND: Pragmatic use of the anti-fibrotic medications pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) in the United States (US) has not been studied and may be different from international settings due to structural differences between health care systems. This study examined the relationship between patient- and site-level characteristics and anti-fibrotic (a) use and (b) selection. METHODS: Data from the Pulmonary Fibrosis Foundation Patient Registry was used to perform univariable and multivariable regressions with generalized linear mixed models. A random effects model examined registry site variation. RESULTS: 703 of 1218 (57.7%) patients were taking a single anti-fibrotic of which 312 (44.4%) were taking nintedanib and 391 (55.6%) were taking pirfenidone. Up to 25% of patients using an anti-fibrotic may have been excluded from clinical trial participation due to having too severe disease as measured by diffusion limitation for carbon monoxide. Age (OR = 0.974, p = 0.0086) and diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 0.896, p = 0.0007) was negatively associated with anti-fibrotic use while time (in log of days) since diagnosis (OR = 1.138, p < 0.0001), recent patient clinical trial participation (OR = 1.569, p = 0.0433) and oxygen use (OR = 1.604, p = 0.0027) was positively associated with anti-fibrotic use. Time (log of days) since diagnosis (OR = 1.075, p = 0.0477), history of coronary artery disease (OR = 1.796, p = 0.0030), presence of pulmonary hypertension (OR = 2.139, p = 0.0376), patient clinical trial participation in the prior 12 months (OR = 2.485, p = 0.0002), diffusion capacity of the lungs for carbon monoxide (per 10% increase in percent-predicted; OR = 1.138, p = 0.0184), anticoagulant use (OR = 2.507, p = 0.0028), and enrollment at a registry site in the Midwest region (OR = 1.600, p = 0.0446) were associated with pirfenidone use. Anti-fibrotic use varied by registry site. Rates of discontinuation were modest and nearly identical for the two medications with side effects being the most common reason given for discontinuation. Twenty-three percent (23%, 274) of persons with IPF were using or had recently used an immunomodulatory agent. CONCLUSIONS: This analysis provides a detailed characterization of IPF treatment patterns in the US; many users of anti-fibrotic medications may not have qualified for inclusion in clinical trials. More research is needed to understand variations in medical decision-making for use and selection of anti-fibrotic medication.

Does hepatobiliary phase sequence qualitatively outperform unenhanced T1-weighted imaging in assessment of the ablation margin 24 hours after thermal ablation of hepatocellular carcinomas?

PURPOSE: To retrospectively determine whether hepatobiliary phase (HBP) sequence outperforms unenhanced T1-weighted imaging (uT1wI) in distinguishing the ablation margin (AM) from hepatocellular carcinoma (HCC) 24 h after thermoablation. MATERIAL AND METHODS: Ninety-one patients [mean age, 65.7 years; 68 M/23F] with 138 HCCs (>6 months follow-up) underwent pre- and postablation gadoxetate disodium-enhanced MRI. AM showed a hyperintense middle zone (MZ) surrounding central hypo- or hyperintense HCCs on uT1wI, and an intermediate-intense MZ encompassing central hypo- or hyperintense HCCs during HBP. The visible AM was defined as persistent MZ around HCCs, which were demarcated from MZ, or peripherally band encompassing MZ, which were not demarcated from HCC. The indefinite AM was defined as no demarcating HCCs from MZ. The ability to distinguish AM from HCC was classified as visible or indefinite on axial (ax)-uT1wI, ax-HBP, coronal (cor)-HBP, and combined all images. To investigate the AM visibility during HBP, significance of differences upon comparison of ax-uT1wI with combined images was analyzed. Preablation liver-tumor contrast ratio (LTCR) on ax-uT1wI and ax-HBP sequence is compared between the visible and indefinite AM. RESULTS: The McNemar test demonstrated a significant increase (p < 0.05) in visible AM from ax-uT1wI (60), to ax-HBP (70), cor-HBP (79), and combined images (83). TLCR with visible AM was significantly higher than that with indefinite AM on ax-uT1wI (0.4 vs. 0.2, p = 0.001) and ax-HBP sequence (0.9 vs. 0.6, p = 0.004). CONCLUSIONS: HBP sequence might have higher feasibility to distinguish AM from tumor than ax-uT1wI. The TLCR value in visible AM was higher than that in indefinite AM on both ax-uT1wI and ax-HBP sequences.

Attenuation-based size metric for estimating organ dose to patients undergoing tube current modulated CT exams.

PURPOSE: Task Group 204 introduced effective diameter (ED) as the patient size metric used to correlate size-specific-dose-estimates. However, this size metric fails to account for patient attenuation properties and has been suggested to be replaced by an attenuation-based size metric, water equivalent diameter (DW). The purpose of this study is to investigate different size metrics, effective diameter, and water equivalent diameter, in combination with regional descriptions of scanner output to establish the most appropriate size metric to be used as a predictor for organ dose in tube current modulated CT exams. METHODS: 101 thoracic and 82 abdomen/pelvis scans from clinically indicated CT exams were collected retrospectively from a multidetector row CT (Sensation 64, Siemens Healthcare) with Institutional Review Board approval to generate voxelized patient models. Fully irradiated organs (lung and breasts in thoracic scans and liver, kidneys, and spleen in abdominal scans) were segmented and used as tally regions in Monte Carlo simulations for reporting organ dose. Along with image data, raw projection data were collected to obtain tube current information for simulating tube current modulation scans using Monte Carlo methods. Additionally, previously described patient size metrics [ED, DW, and approximated water equivalent diameter (DWa)] were calculated for each patient and reported in three different ways: a single value averaged over the entire scan, a single value averaged over the region of interest, and a single value from a location in the middle of the scan volume. Organ doses were normalized by an appropriate mAs weighted CTDIvol to reflect regional variation of tube current. Linear regression analysis was used to evaluate the correlations between normalized organ doses and each size metric. RESULTS: For the abdominal organs, the correlations between normalized organ dose and size metric were overall slightly higher for all three differently (global, regional, and middle slice) reported DW and DWa than they were for ED, but the differences were not statistically significant. However, for lung dose, computed correlations using water equivalent diameter calculated in the middle of the image data (DW,middle) and averaged over the low attenuating region of lung (DW,regional) were statistically significantly higher than correlations of normalized lung dose with ED. CONCLUSIONS: To conclude, effective diameter and water equivalent diameter are very similar in abdominal regions; however, their difference becomes noticeable in lungs. Water equivalent diameter, specifically reported as a regional average and middle of scan volume, was shown to be better predictors of lung dose. Therefore, an attenuation-based size metric (water equivalent diameter) is recommended because it is more robust across different anatomic regions. Additionally, it was observed that the regional size metric reported as a single value averaged over a region of interest and the size metric calculated from a single slice/image chosen from the middle of the scan volume are highly correlated for these specific patient models and scan types.

The feasibility of a regional CTDIvol to estimate organ dose from tube current modulated CT exams.

PURPOSE: In AAPM Task Group 204, the size-specific dose estimate (SSDE) was developed by providing size adjustment factors which are applied to the Computed Tomography (CT) standardized dose metric, CTDI(vol). However, that work focused on fixed tube current scans and did not specifically address tube current modulation (TCM) scans, which are currently the majority of clinical scans performed. The purpose of this study was to extend the SSDE concept to account for TCM by investigating the feasibility of using anatomic and organ specific regions of scanner output to improve accuracy of dose estimates. METHODS: Thirty-nine adult abdomen/pelvis and 32 chest scans from clinically indicated CT exams acquired on a multidetector CT using TCM were obtained with Institutional Review Board approval for generating voxelized models. Along with image data, raw projection data were obtained to extract TCM functions for use in Monte Carlo simulations. Patient size was calculated using the effective diameter described in TG 204. In addition, the scanner-reported CTDI(vo)l (CTDI(vol),global) was obtained for each patient, which is based on the average tube current across the entire scan. For the abdomen/pelvis scans, liver, spleen, and kidneys were manually segmented from the patient datasets; for the chest scans, lungs and for female models only, glandular breast tissue were segmented. For each patient organ doses were estimated using Monte Carlo Methods. To investigate the utility of regional measures of scanner output, regional and organ anatomic boundaries were identified from image data and used to calculate regional and organ-specific average tube current values. From these regional and organ-specific averages, CTDI(vol) values, referred to as regional and organ-specific CTDI(vol), were calculated for each patient. Using an approach similar to TG 204, all CTDI(vol) values were used to normalize simulated organ doses; and the ability of each normalized dose to correlate with patient size was investigated. RESULTS: For all five organs, the correlations with patient size increased when organ doses were normalized by regional and organ-specific CTDI(vol) values. For example, when estimating dose to the liver, CTDI(vol),global yielded a R(2) value of 0.26, which improved to 0.77 and 0.86, when using the regional and organ-specific CTDI(vol) for abdomen and liver, respectively. For breast dose, the global CTDI(vol) yielded a R(2) value of 0.08, which improved to 0.58 and 0.83, when using the regional and organ-specific CTDI(vol) for chest and breasts, respectively. The R(2) values also increased once the thoracic models were separated for the analysis into females and males, indicating differences between genders in this region not explained by a simple measure of effective diameter. CONCLUSIONS: This work demonstrated the utility of regional and organ-specific CTDI(vol) as normalization factors when using TCM. It was demonstrated that CTDI(vol),global is not an effective normalization factor in TCM exams where attenuation (and therefore tube current) varies considerably throughout the scan, such as abdomen/pelvis and even thorax. These exams can be more accurately assessed for dose using regional CTDI(vol) descriptors that account for local variations in scanner output present when TCM is employed.

A comparison of methods to estimate organ doses in CT when utilizing approximations to the tube current modulation function.

PURPOSE: Most methods to estimate patient dose from computed tomography (CT) exams have been developed based on fixed tube current scans. However, in current clinical practice, many CT exams are performed using tube current modulation (TCM). Detailed information about the TCM function is difficult to obtain and therefore not easily integrated into patient dose estimate methods. The purpose of this study was to investigate the accuracy of organ dose estimates obtained using methods that approximate the TCM function using more readily available data compared to estimates obtained using the detailed description of the TCM function. METHODS: Twenty adult female models generated from actual patient thoracic CT exams and 20 pediatric female models generated from whole body PET∕CT exams were obtained with IRB (Institutional Review Board) approval. Detailed TCM function for each patient was obtained from projection data. Monte Carlo based models of each scanner and patient model were developed that incorporated the detailed TCM function for each patient model. Lungs and glandular breast tissue were identified in each patient model so that organ doses could be estimated from simulations. Three sets of simulations were performed: one using the original detailed TCM function (x, y, and z modulations), one using an approximation to the TCM function (only the z-axis or longitudinal modulation extracted from the image data), and the third was a fixed tube current simulation using a single tube current value which was equal to the average tube current over the entire exam. Differences from the reference (detailed TCM) method were calculated based on organ dose estimates. Pearson's correlation coefficients were calculated between methods after testing for normality. Equivalence test was performed to compare the equivalence limit between each method (longitudinal approximated TCM and fixed tube current method) and the detailed TCM method. Minimum equivalence limit was reported for each organ. RESULTS: Doses estimated using the longitudinal approximated TCM resulted in small differences from doses obtained using the detailed TCM function. The calculated root-mean-square errors (RMSE) for adult female chest simulations were 9% and 3% for breasts and lungs, respectively; for pediatric female chest and whole body simulations RMSE were 9% and 7% for breasts and 3% and 1% for lungs, respectively. Pearson's correlation coefficients were consistently high for the longitudinal approximated TCM method, ranging from 0.947 to 0.999, compared to the fixed tube current value ranging from 0.8099 to 0.9916. In addition, an equivalence test illustrated that across all models the longitudinal approximated TCM is equivalent to the detailed TCM function within up to 3% for lungs and breasts. CONCLUSIONS: While the best estimate of organ dose requires the detailed description of the TCM function for each patient, extracting these values can be difficult. The presented results show that an approximation using available data extracted from the DICOM header provides organ dose estimates with RMSE of less than 10%. On the other hand, the use of the overall average tube current as a single tube current value was shown to result in poor and inconsistent estimates of organ doses.

Computer-aided quantitative bone scan assessment of prostate cancer treatment response.

OBJECTIVE: The development and evaluation of a computer-aided bone scan analysis technique to quantify changes in tumor burden and assess treatment effects in prostate cancer clinical trials. METHODS: We have developed and report on a commercial fully automated computer-aided detection (CAD) system. Using this system, scan images were intensity normalized, and then lesions were identified and segmented by anatomic region-specific intensity thresholding. Detected lesions were compared against expert markings to assess the accuracy of the CAD system. The metrics Bone Scan Lesion Area, Bone Scan Lesion Intensity, and Bone Scan Lesion Count were calculated from identified lesions, and their utility in assessing treatment effects was evaluated by analyzing before and after scans from metastatic castration-resistant prostate cancer patients: 10 treated and 10 untreated. In this study, patients were treated with cabozantinib, a MET/vascular endothelial growth factor inhibitor resulting in high rates of resolution of bone scan abnormalities. RESULTS: Our automated CAD system identified bone lesion pixels with 94% sensitivity, 89% specificity, and 89% accuracy. Significant differences in changes from baseline were found between treated and untreated groups in all assessed measurements derived by our system. The most significant measure, Bone Scan Lesion Area, showed a median (interquartile range) change from baseline at week 6 of 7.13% (27.61) in the untreated group compared with -73.76% (45.38) in the cabozantinib-treated group (P=0.0003). CONCLUSION: Our system accurately and objectively identified and quantified metastases in bone scans, allowing for interpatient and intrapatient comparison. It demonstrates potential as an objective measurement of treatment effects, laying the foundation for validation against other clinically relevant outcome measures.

Quantitative texture-based assessment of one-year changes in fibrotic reticular patterns on HRCT in scleroderma lung disease treated with oral cyclophosphamide.

OBJECTIVES: The Scleroderma Lung Study showed the efficacy of cyclophosphamide in modestly improving the forced vital capacity (FVC) compared with placebo over 1 year. Using changes in texture-based scores that quantify lung fibrosis as the percentage involvement of reticulation patterns, the effectiveness of cyclophosphamide was re-assessed by examining its impact on quantitative lung fibrosis (QLF). METHODS: Axial HRCT images were acquired (1-mm slice thickness, 10-mm increments) in the prone position at inspiration. A validated model for quantifying interstitial disease patterns was applied to images from 83 subjects at baseline and 12 months. Scores were calculated for six zones (upper, mid, lower of the right/left lung) and the whole lung. Average changes were compared. Correlations were performed between QLF and physiological and clinical scores. RESULTS: From the most severe zones identified at baseline, QLF scores decreased by 2.6% in the cyclophosphamide group, whereas they increased by 9.1% in the placebo group, leading to ~12% difference (p = 0.0027). Between-treatment difference in whole lung QLF was ~5% (p = 0.0190). Significant associations were observed between changes in QLF and FVC (r = -0.33), dyspnea score (r = -0.29), and consensus visual score (p = 0.0001). CONCLUSIONS: QLF scores provide an objective quantitative tool for assessing treatment efficacy in scleroderma-related interstitial lung disease.

A method to generate equivalent energy spectra and filtration models based on measurement for multidetector CT Monte Carlo dosimetry simulations.

The purpose of this study was to present a method for generating x-ray source models for performing Monte Carlo (MC) radiation dosimetry simulations of multidetector row CT (MDCT) scanners. These so-called "equivalent" source models consist of an energy spectrum and filtration description that are generated based wholly on the measured values and can be used in place of proprietary manufacturer's data for scanner-specific MDCT MC simulations. Required measurements include the half value layers (HVL1 and HVL2) and the bowtie profile (exposure values across the fan beam) for the MDCT scanner of interest. Using these measured values, a method was described (a) to numerically construct a spectrum with the calculated HVLs approximately equal to those measured (equivalent spectrum) and then (b) to determine a filtration scheme (equivalent filter) that attenuates the equivalent spectrum in a similar fashion as the actual filtration attenuates the actual x-ray beam, as measured by the bowtie profile measurements. Using this method, two types of equivalent source models were generated: One using a spectrum based on both HVL1 and HVL2 measurements and its corresponding filtration scheme and the second consisting of a spectrum based only on the measured HVL1 and its corresponding filtration scheme. Finally, a third type of source model was built based on the spectrum and filtration data provided by the scanner's manufacturer. MC simulations using each of these three source model types were evaluated by comparing the accuracy of multiple CT dose index (CTDI) simulations to measured CTDI values for 64-slice scanners from the four major MDCT manufacturers. Comprehensive evaluations were carried out for each scanner using each kVp and bowtie filter combination available. CTDI experiments were performed for both head (16 cm in diameter) and body (32 cm in diameter) CTDI phantoms using both central and peripheral measurement positions. Both equivalent source model types result in simulations with an average root mean square (RMS) error between the measured and simulated values of approximately 5% across all scanner and bowtie filter combinations, all kVps, both phantom sizes, and both measurement positions, while data provided from the manufacturers gave an average RMS error of approximately 12% pooled across all conditions. While there was no statistically significant difference between the two types of equivalent source models, both of these model types were shown to be statistically significantly different from the source model based on manufacturer's data. These results demonstrate that an equivalent source model based only on measured values can be used in place of manufacturer's data for Monte Carlo simulations for MDCT dosimetry.