Lung Cancer Screening Eligibility and Use: A Population Health Perspective of One Community.

BACKGROUND Low-dose chest CT (LDCT) is the only effective screening test for lung cancer. Annual lung cancer screening (LCS) is recommended by the US Preventive Services Task Force (USPSTF) for individuals at high risk for primary lung neoplasm.METHODS We retrospectively identified patients receiving LCS from January 2016 through March 2018 whose residential addresses were within our health center's county. We estimated driving distance from the patient's address to our health center and obtained sociodemographic characteristics from the electronic health record (EHR). The census-tract-level LCS-eligible population size was estimated, and their population characteristics determined via US Census Bureau, Centers for Disease Control and Prevention (CDC), and Behavioral Risk Factor Surveillance System (BRFSS) data. The Cochran-Mantel-Haenszel test was used to determine differences amongst the LCS-eligible and LCS-enrolled populations. Multivariable regression was used to determine the effects of sociodemographic characteristics on LCS eligibility.RESULTS There was modest correlation between census-tract-level LCS-eligible population size and LCS enrollment (r = 0.68, P < .001). 5.9% (364/6185) of the estimated LCS-eligible population in our county received LCS, with census-tract LCS rates ranging from 1.5% to 12.5%. Nonwhite race status (Hispanic and African American) was associated with decreased likelihood of LCS enrollment compared to White race (OR = 95% CI, 0.765 [0.61, 0.95] and 0.031 [0.008, 0.124], respectively). Older age, Medicaid, and uninsured statuses were positively correlated with LCS eligibility (P ≤ .01).LIMITATIONS This analysis comprises a single county. Other LCS facilities within our health system in neighboring counties, as well as individuals receiving LCS outside of our health system, are not captured.CONCLUSIONS The uptake of LCS remains low, with disproportionately lower screening rates amongst Hispanic and African American populations. Medicaid and uninsured patients in our community are also more likely to be LCS-eligible. These populations may be targets for interventions aimed at increasing LCS awareness and uptake.

Long-term evolution of LI-RADS observations in HCV-related cirrhosis treated with direct-acting antivirals.

BACKGROUND & AIMS: The risk of progression of indeterminate observations to hepatocellular carcinoma (HCC) after direct-acting antivirals (DAA) is still undetermined. To assess whether DAA therapy changes the risk of progression of observations with low (LR-2), intermediate (LR-3) and high (LR-4) probability for HCC in cirrhotic patients and to identify predictors of progression. METHODS: This retrospective study included cirrhotic patients treated with DAA who achieved sustained virological response between 2015 and 2019. A total of 68 patients had pre-DAA indeterminate observations and at least six months CT/MRI follow-up before and after DAA. Two radiologists reviewed CT/MRI studies to categorize observations according to the LI-RADSv2018 and assess the evolution on subsequent follow-ups. Predictors of evolutions were evaluated by using the Cox proportional hazard model, Kaplan-Meier method and log-rank test. RESULTS: A total of 109 untreated observations were evaluated, including 31 (28.4%) LR-2, 67 (61.5%) LR-3 and 11 (10.1%) LR-4. During a median follow-up of 41 months, 17.4% and 13.3% of observations evolved to LR-5 or LR-M and LR-5, before and after DAA respectively (P = .428). There was no difference in rate of progression of neither LR-2 (P = 1.000), LR-3 (P = .833) or LR-4 (P = .505). At multivariate analysis, only initial LI-RADS category was an independent predictor of progression to LR-5 or LR-M for all observations (hazard ratio 6.75, P < .001), and of progression to LR-5 after DAA (hazard ratio 4.34, P = .047). CONCLUSIONS: DAA therapy does not increase progression of indeterminate observations to malignant categories. The initial LI-RADS category is an independent predictor of observations upgrade.

Patient-Informed Organ Dose Estimation in Clinical CT: Implementation and Effective Dose Assessment in 1048 Clinical Patients.

OBJECTIVE. The purpose of this study is to comprehensively implement a patient-informed organ dose monitoring framework for clinical CT and compare the effective dose (ED) according to the patient-informed organ dose with ED according to the dose-length product (DLP) in 1048 patients. MATERIALS AND METHODS. Organ doses for a given examination are computed by matching the topogram to a computational phantom from a library of anthropomorphic phantoms and scaling the fixed tube current dose coefficients by the examination volume CT dose index (CTDIvol) and the tube-current modulation using a previously validated convolution-based technique. In this study, the library was expanded to 58 adult, 56 pediatric, five pregnant, and 12 International Commission on Radiological Protection (ICRP) reference models, and the technique was extended to include multiple protocols, a bias correction, and uncertainty estimates. The method was implemented in a clinical monitoring system to estimate organ dose and organ dose-based ED for 647 abdomen-pelvis and 401 chest examinations, which were compared with DLP-based ED using a t test. RESULTS. For the majority of the organs, the maximum errors in organ dose estimation were 18% and 8%, averaged across all protocols, without and with bias correction, respectively. For the patient examinations, DLP-based ED was significantly different from organ dose-based ED by as much as 190.9% and 234.7% for chest and abdomen-pelvis scans, respectively (mean, 9.0% and 24.3%). The differences were statistically significant (p < .001) and exhibited overestimation for larger-sized patients and underestimation for smaller-sized patients. CONCLUSION. A patient-informed organ dose estimation framework was comprehensively implemented applicable to clinical imaging of adult, pediatric, and pregnant patients. Compared with organ dose-based ED, DLP-based ED may overestimate effective dose for larger-sized patients and underestimate it for smaller-sized patients.

Radiological Society of North America/Quantitative Imaging Biomarker Alliance Shear Wave Speed Bias Quantification in Elastic and Viscoelastic Phantoms.

OBJECTIVES: To quantify the bias of shear wave speed (SWS) measurements between different commercial ultrasonic shear elasticity systems and a magnetic resonance elastography (MRE) system in elastic and viscoelastic phantoms. METHODS: Two elastic phantoms, representing healthy through fibrotic liver, were measured with 5 different ultrasound platforms, and 3 viscoelastic phantoms, representing healthy through fibrotic liver tissue, were measured with 12 different ultrasound platforms. Measurements were performed with different systems at different sites, at 3 focal depths, and with different appraisers. The SWS bias across the systems was quantified as a function of the system, site, focal depth, and appraiser. A single MRE research system was also used to characterize these phantoms using discrete frequencies from 60 to 500 Hz. RESULTS: The SWS from different systems had mean difference 95% confidence intervals of ±0.145 m/s (±9.6%) across both elastic phantoms and ± 0.340 m/s (±15.3%) across the viscoelastic phantoms. The focal depth and appraiser were less significant sources of SWS variability than the system and site. Magnetic resonance elastography best matched the ultrasonic SWS in the viscoelastic phantoms using a 140 Hz source but had a - 0.27 ± 0.027-m/s (-12.2% ± 1.2%) bias when using the clinically implemented 60-Hz vibration source. CONCLUSIONS: Shear wave speed reconstruction across different manufacturer systems is more consistent in elastic than viscoelastic phantoms, with a mean difference bias of < ±10% in all cases. Magnetic resonance elastographic measurements in the elastic and viscoelastic phantoms best match the ultrasound systems with a 140-Hz excitation but have a significant negative bias operating at 60 Hz. This study establishes a foundation for meaningful comparison of SWS measurements made with different platforms.

Risk of erectile dysfunction after modern radiotherapy for intact prostate cancer.

BACKGROUND: Erectile dysfunction (ED) is a prevalent side effect of prostate cancer treatment. We hypothesized that the previously reported rates of ED may have improved with the advent of modern technology. The purpose of this project was to evaluate modern external beam radiotherapy and brachytherapy techniques to determine the incidence of radiotherapy (RT) induced ED. METHODS: A systematic review of the literature published between January 2002 and December 2018 was performed to obtain patient reported rates of ED after definitive external beam radiotherapy, ultrafractionated stereotactic radiotherapy, and brachytherapy (BT) to the prostate in men who were potent prior to RT. Univariate and multivariate analyses of radiation dose, treatment strategy, and length of follow-up were analyzed to ascertain their relationship with RT-induced ED. RESULTS: Of 890 articles reviewed, 24 met inclusion criteria, providing data from 2714 patients. Diminished erectile function status post RT was common and similar across all studies. The median increase in men reporting ED was 17%, 26%, 23%, and 23%, 3DCRT, IMRT, low dose rate BT, and SBRT, respectively, at 2-year median follow-up. CONCLUSION: ED is a common side effect of RT. Risk of post-RT ED is similar for both LDR brachytherapy and external beam RT with advanced prostate targeting and penile-bulb sparing techniques utilized in modern RT techniques.

Early 18F-FDG-PET Response During Radiation Therapy for HPV-Related Oropharyngeal Cancer May Predict Disease Recurrence.

PURPOSE: Early indication of treatment outcome may guide therapeutic de-escalation strategies in patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC). This study investigated the relationships between tumor volume and 18F-fluorodeoxyglucose positron emission tomography (PET) parameters before and during definitive radiation therapy with treatment outcomes. METHODS AND MATERIALS: Patients undergoing definitive (chemo)radiation for HPV-related/p16-positive OPC were prospectively enrolled on an institutional review board-approved study. 18F-fluorodeoxyglucose PET/computed tomography scans were performed at simulation and after 2 weeks at a dose of ∼20 Gy. Tumor volume and standardized uptake value (SUV) characteristics were measured. SUV was normalized to blood pool uptake. Tumor volume and PET parameters associated with recurrence were identified through recursive partitioning (RPART). Recurrence-free survival (RFS) and overall survival (OS) curves between RPART-identified cohorts were estimated using the Kaplan-Meier method, and Cox models were used to estimate the hazard ratios (HRs). RESULTS: From 2012 to 2016, 62 patients with HPV-related OPC were enrolled. Median follow-up was 4.4 years. RPART identified patients with intratreatment SUVmax (normalized to blood pool SUVmean) <6.7 or SUVmax (normalized to blood pool SUVmean) ≥6.7 with intratreatment SUV40% ≥2.75 as less likely to recur. For identified subgroups, results of Cox models showed unadjusted HRs for RFS and OS (more likely to recur vs less likely) of 7.33 (90% confidence interval [CI], 2.97-18.12) and 6.09 (90% CI, 2.22-16.71), respectively, and adjusted HRs of 6.57 (90% CI, 2.53-17.05) and 5.61 (90% CI, 1.90-16.54) for RFS and OS, respectively. CONCLUSIONS: PET parameters after 2 weeks of definitive radiation therapy for HPV-related OPC are associated with RFS and OS, thus potentially informing an adaptive treatment approach.

Sample size requirements for detecting treatment effect heterogeneity in cluster randomized trials.

Cluster randomized trials (CRTs) refer to experiments with randomization carried out at the cluster or the group level. While numerous statistical methods have been developed for the design and analysis of CRTs, most of the existing methods focused on testing the overall treatment effect across the population characteristics, with few discussions on the differential treatment effect among subpopulations. In addition, the sample size and power requirements for detecting differential treatment effect in CRTs remain unclear, but are helpful for studies planned with such an objective. In this article, we develop a new sample size formula for detecting treatment effect heterogeneity in two-level CRTs for continuous outcomes, continuous or binary covariates measured at cluster or individual level. We also investigate the roles of two intraclass correlation coefficients (ICCs): the adjusted ICC for the outcome of interest and the marginal ICC for the covariate of interest. We further derive a closed-form design effect formula to facilitate the application of the proposed method, and provide extensions to accommodate multiple covariates. Extensive simulations are carried out to validate the proposed formula in finite samples. We find that the empirical power agrees well with the prediction across a range of parameter constellations, when data are analyzed by a linear mixed effects model with a treatment-by-covariate interaction. Finally, we use data from the HF-ACTION study to illustrate the proposed sample size procedure for detecting heterogeneous treatment effects.

Utilization of Lung Cancer Screening in the Medicare Fee-for-Service Population.

BACKGROUND: A number of organizations, including the US Preventive Services Task Force (USPSTF), recommend lung cancer screening (LCS) with low-dose CT (LDCT) imaging for high-risk current and former smokers. In 2015, Medicare issued a decision to cover LCS as a preventive health benefit; however, utilization by the Medicare population has not been thoroughly examined. RESEARCH QUESTION: Our objective was to evaluate the early use of LCS in the Medicare fee-for-service (FFS) population and determine the relationship(s) among beneficiary sociodemographic characteristics, geographic location, and use. STUDY DESIGN AND METHODS: This cross-sectional observational study used 100% Medicare FFS claims files for Medicare beneficiaries receiving LCS between January 1, 2016 and December 31, 2016. We estimated the LCS-eligible Medicare population using population and smoking data from the US Census Bureau and Centers for Disease Control and Prevention. We assessed variation in LCS rates by beneficiary characteristics and geography, using univariate and multivariate regression, the latter also including how interactions between geographic location and race/ethnicity influence screening. RESULTS: A total of 103,892 Medicare FFS beneficiaries received LCS in 2016, comprising 4.1% (95% CI, 3.9%-4.3%) of the estimated LCS-eligible Medicare population. Accounting for the interactions between race/ethnicity and US region, nonwhite (black, Hispanic) beneficiaries in all US regions were screened with lower frequency than white beneficiaries (P < .001). Screening rates in the Northeast were significantly higher than in other regions (adjusted rate ratio [95% CI] of Northeast relative to South: 1.83 [1.36-2.46]). INTERPRETATION: The early adoption of LCS among Medicare beneficiaries was low. Our results suggest geographic and racial disparities in screening use, with populations in the South and those of nonwhite race/ethnicity being screened with lower frequency. Further work is needed to improve LCS uptake and ensure consistent use by all at-risk populations.

Hepatobiliary phase hypointensity predicts progression to hepatocellular carcinoma for intermediate-high risk observations, but not time to progression.

PURPOSE: To determine whether hepatobiliary phase hypointensity, enhancing "capsule" and size provide prognostic information regarding the risk of progression to hepatocellular carcinoma (HCC), as well as the time to progression, of intermediate to high risk observations ≥ 10 mm with arterial phase hyperenhancement (APHE). METHOD: This retrospective dual-institution study included 160 LR-3 and 26 LR-4 observations measuring more than 10 mm and having APHE in 136 patients (mean age [SD], 57 [11] years old). A composite reference standard of pathologic analysis and imaging follow-up was used. The prognostic performance of hepatobiliary phase hypointensity, enhancing "capsule" and size (cut-off: 20 mm) for the prediction of probability of progression to HCC and median time to progression to HCC was assessed and compared by means of Log-rank test, Cox-regression and Kaplan-Meier curves. RESULTS: 110 (59%) of 186 of observations progressed to HCC, 29.1% (32) progressed within 6 months, 60% (66) within 1 year and 84.5% (93) within 2 years. Hepatobiliary phase hypointensity was a significant predictor of progression to HCC (p < 0.0001, odds ratio: 20.62) but not of time to progression (p = 0.17). Median time to progression to HCC was 284 days [IQR: 266-363] and was shorter - though not significantly - for observations with enhancing "capsule" (118 days vs 301 days; p = 0.19). CONCLUSIONS: Hepatobiliary phase hypointensity is an independent predictor of progression to HCC in intermediate to high risk APHE observations ≥ 10 mm.

Long-term Evolution of Hepatocellular Adenomas at MRI Follow-up.

Background Hepatocellular adenomas (HCAs) are rare benign liver tumors. Guidelines recommend continued surveillance of patients diagnosed with HCAs, but these guidelines are mainly based on small studies or expert opinion. Purpose To analyze the long-term evolution of HCAs, including solitary and multiple lesions, and to identify predictive features of progression with MRI. Materials and Methods In a retrospective study, patients diagnosed with pathologically proven solitary or multiple HCAs between January 2004 and December 2015 were included; ß-catenin-mutated HCAs and HCAs with foci of malignancy were considered to be at risk for progression. MRI examinations were analyzed, and tumor evolution was evaluated by using Response Evaluation Criteria in Solid Tumors, version 1.1. Student t, Mann-Whitney, χ2, Fisher exact, and McNemar tests were used, as appropriate. Results In total, 118 patients (mean age, 40 years ± 10 [standard deviation]; 108 women) were evaluated, including 41 with a solitary HCA (mean age, 40 years ± 14; 36 women) and 77 with multiple HCAs (mean age, 40 years ± 10; 72 women). At a median follow-up of 5 years, 37 of 41 (90%) patients with a solitary HCA and 55 of 77 (71%) patients with multiple HCAs showed stable or regressive disease. After resection of solitary HCAs, new lesions appeared in only two of 29 (7%) patients, both of whom had HCAs at risk of progression. In patients with multiple HCAs, hepatocyte nuclear factor 1α-inactivated HCAs showed a higher rate of progression compared with inflammatory HCAs (11 of 26 [42%] vs seven of 37 [19%], P = .04) despite lower use (28 of 32 patients [88%] vs 45 of 45 patients [100%]; P = .03) and shorter duration (mean, 12.0 years ± 7.5 vs 19.2 years ± 9.2; P = .001) of oral contraceptive intake. Conclusion Long-term MRI follow-up showed that 78% of hepatocellular adenomas had long-term stability or regression. After resection of solitary hepatocellular adenomas, new lesions occurred only in hepatocellular adenomas at risk of progression. Patients with multiple hepatocellular adenomas were more likely to show progressive disease, with hepatic nuclear factor 1α-inactivated hepatocellular adenomas being the most common subtype showing progression. © RSNA, 2020 Online supplemental material is available for this article.

Liver Imaging Reporting and Data System (LI-RADS) v2018: diagnostic value of ancillary features favoring malignancy in hypervascular observations ≥ 10 mm at intermediate (LR-3) and high probability (LR-4) for hepatocellular carcinoma.

OBJECTIVE: This study was conducted in order to assess the diagnostic accuracy of LI-RADS v2018 ancillary features (AFs) favoring malignancy applied to LR-3 and LR-4 observations on gadoxetate-enhanced MRI. METHODS: In this retrospective dual-institution study, we included consecutive patients at high risk for hepatocellular carcinoma (HCC) imaged with gadoxetate disodium-enhanced MRI between 2009 and 2014 fulfilling the following criteria: (i) at least one LR-3 or LR-4 observation ≥ 10 mm; (ii) nonrim arterial phase hyperenhancement; and (iii) confirmation of benignity or malignancy by pathology or imaging follow-up. We compared the distribution of AFs between HCCs and benign observations and the diagnostic performance for the diagnosis of HCC using univariate and multivariate analyses. Significance was set at p value < 0.05. RESULTS: Two hundred five observations were selected in 155 patients (108 M, 47 F) including 167 (81.5%) LR-3 and 38 (18.5%) LR-4. There were 126 (61.5%) HCCs and 79 (28.5%) benign lesions. A significantly larger number of AFs favoring malignancy were found in LR-3 and LR-4 lesions that progressed to HCC compared to benign lesions (p < 0.001 and p = 0.003, respectively). The most common AFs favoring malignancy in HCCs were hepatobiliary phase (HBP) hypointensity (p < 0.001), transitional phase hypointensity (p < 0.001), and mild-moderate T2 hyperintensity (p < 0.001). Sensitivity and specificity of AFs for the diagnosis of HCC ranged 0.8-76.2% and 86.1-100%, respectively. HBP hypointensity yielded the highest sensitivity but also the lowest specificity and was the only AF remaining independently associated with the diagnosis of HCC at multivariate logistic regression analysis (OR 14.83, 95% CI 5.81-42.76, p < 0.001). CONCLUSIONS: Among all AFs, HBP hypointensity yields the highest sensitivity for the diagnosis of HCC. KEY POINTS: • LR-3 and LR-4 observations diagnosed as HCC have a significantly higher number of ancillary features favoring malignancy compared to observations proven to be benign. • The presence of three or more ancillary features favoring malignancy has a high specificity (96.2%) for the diagnosis of HCC. • Among all ancillary features favoring malignancy, hepatobiliary phase hypointensity yields the highest sensitivity, but also the lowest specificity for the diagnosis of HCC.

Influence of background lung characteristics on nodule detection with computed tomography.

We sought to characterize local lung complexity in chest computed tomography (CT) and to characterize its impact on the detectability of pulmonary nodules. Forty volumetric chest CT scans were created by embedding between three and five simulated 5-mm lung nodules into one of three volumetric chest CT datasets. Thirteen radiologists evaluated 157 nodules, resulting in 2041 detection opportunities. Analyzing the substrate CT data prior to nodule insertion, 14 image features were measured within a region around each nodule location. A generalized linear mixed-effects statistical model was fit to the data to verify the contribution of each metric on detectability. The model was tuned for simplicity, interpretability, and generalizability using stepwise regression applied to the primary features and their interactions. We found that variables corresponding to each of five categories (local structural distractors, local intensity, global context, local vascularity, and contiguity with structural distractors) were significant ( p < 0.01 ) factors in a standardized model. Moreover, reader-specific models conveyed significant differences among readers with significant distraction (missed detections) influenced by local intensity- versus local-structural characteristics being mutually exclusive. Readers with significant local intensity distraction ( n = 10 ) detected substantially fewer lung nodules than those who were significantly distracted by local structure ( n = 2 ), 46.1% versus 65.3% mean nodules detected, respectively.

Impact of baseline covariate imbalance on bias in treatment effect estimation in cluster randomized trials: Race as an example.

Individual-level baseline covariate imbalance could happen more frequently in cluster randomized trials, and may influence the observed treatment effect. Using computer and real-data simulations, this paper quantifies the extent and impact of covariate imbalance on the estimated treatment effect for both continuous and binary outcomes, and relates it to the degree of imbalance for different numbers of clusters, cluster sizes, and covariate intraclass correlation coefficients. We focused on the impact of race as a covariate, given the emphasis of regulatory and funding bodies on understanding the influence of demographic characteristics on treatment effectiveness. We found that bias in the treatment effect is proportional to both the degree of baseline covariate imbalance and the covariate effect size. Larger numbers of clusters result in lower covariate imbalance, and increasing cluster size is less effective in reducing imbalance compared to increasing the number of clusters. Models adjusted for important baseline confounders are superior to unadjusted models for minimizing bias in both model-based simulations and an innovative simulation based on real clinical trial data. Higher outcome intraclass correlation coefficients did not affect bias but resulted in greater variance in treatment estimates.

Impact of Colorized Display of Mammograms on Lesion Detection.

OBJECTIVE: To assess the effect of the colorized display of digital mammograms on observer detection of subtle breast lesions. METHODS: Three separate observer studies compared detection performance using grayscale versus color display of 1) low-contrast mass-like objects in a standardized mammography phantom; 2) simulated microcalcifications in a background of normal breast parenchyma; and 3) standard-of-care clinical digital mammograms with subtle calcifications and masses. Colorization of the images was done by displaying each image pixel in blue, green, and red hues, or gray, maintaining DICOM-calibrated luminance scale and consistent luminance range. For the simulated calcifications and clinical mammogram studies, comparison of detection rates was computed using McNemar's test for paired differences. RESULTS: For the phantom study, mass-like object detection was significantly better using a green colormap than grayscale (73.3% vs 70.8%, P = .009), with no significant improvement using blue or red colormaps (72.6% and 72.5%, respectively). For simulated microcalcifications, no significant difference was noted in detection using the green colormap, as compared with grayscale. For clinical digital screening mammograms, no significant difference was noted between gray and green colormaps for detection of microcalcifications. Green color display, however, resulted in decreased sensitivity for detection of subtle masses (63% vs 69%, P = .03). CONCLUSION: Although modest improvement was demonstrated for a detection task using colorized display of a standard mammography phantom, no significant improvement was demonstrated using a color display for a simulated clinical detection task, and actual clinical performance was worse for colorized display of mammograms in comparison to standard grayscale display.

Assessing heterogeneity of treatment effect analyses in health-related cluster randomized trials: A systematic review.

BACKGROUND: Cluster-randomized trials (CRTs) are being increasingly used to test a range of interventions, including medical interventions commonly used in clinical practice. Policies created by the NIH and the Food and Drug Administration (FDA) require the reporting of demographics and the examination of demographic heterogeneity of treatment effect (HTE) for individually randomized trials. Little is known about how frequent demographics are reported and HTE analyses are conducted in CRTs. OBJECTIVES: We sought to understand the prevalence of HTE analyses and the statistical methods used to conduct them in CRTs focused on treating cardiovascular disease, cancer, and chronic lower respiratory diseases. Additionally, we also report on the proportion of CRTs that reported on baseline demographics of its populations and conducted demographic HTE analyses. DATA SOURCES: We searched PubMed and Embase for CRTs published between 1/1/2010 and 3/29/2016 that focused on treating the top 3 Center for Disease Control causes of death (cardiovascular disease, chronic lower respiratory disease, and cancer). Evidence Screening And Review: Of 1,682 unique titles, 117 abstracts were screened. After excluding 53 articles, we included 64 CRT publications and abstracted information on study characteristics and demographic information, statistical analysis, HTE analysis, and study quality. RESULTS: Age and sex were reported in greater than 95.3% of CRTs, while race and ethnicity were reported in only 20.3% of CRTs. HTE analyses were conducted in 28.1% (n = 18) of included CRTs and 77.8% (n = 12) were prespecified analyses. Four CRTs conducted a demographic subgroup analysis. Only 6/18 CRTs used interaction testing to determine whether HTE existed. CONCLUSIONS: Baseline demographic reporting was high for age and sex in CRTs, but was uncommon for race and ethnicity. HTE analyses were uncommon and was rare for demographic subgroups, which limits the ability to examine the extent of benefits or risks for treatments tested with CRT designs.

A Geospatial Analysis of Factors Affecting Access to CT Facilities: Implications for Lung Cancer Screening.

OBJECTIVE: The association between access to CT facilities for lung cancer screening and population characteristics is understudied. We aimed to determine the relationship between census tract-level socioeconomic characteristics (SEC) and driving distance to an ACR-accredited CT facility. METHODS: Census tract-level SEC were determined from the US Census Bureau. Distance to nearest ACR-accredited CT facility was derived at the census tract level. Census tract-level multivariable regression modeling was used to determine the relationship between driving distance to a CT facility and census tract SEC, including population density (a marker of rural versus urban), gender, race, insurance status or type, and education level. RESULTS: In an adjusted multivariable model, census tract-level population density was the greatest relative determinant of distance to a CT facility. Namely, rural census tracts had relatively longer distances to CT facilities than urban census tracts (P < .001). Census tracts with higher uninsured, Medicaid, undereducated (less

Retrospective analysis of safety and efficacy of anti-PD-1 therapy and radiation therapy in advanced melanoma: A bi-institutional study.

BACKGROUND AND PURPOSE: Antibodies against programmed cell death protein 1 (PD-1) are standard treatments for advanced melanoma. Palliative radiation therapy (RT) is commonly administered for this disease. Safety and optimal timing for this combination for melanoma has not been established. MATERIALS AND METHODS: In this retrospective cohort study, records for melanoma patients who received anti-PD-1 therapy at Duke University or Emory University (1/1/2013-12/30/2015) were reviewed. Patients were categorized by receipt of RT and RT timing relative to anti-PD-1. RESULTS: 151 patients received anti-PD-1 therapy. Median follow-up was 12.9 months. Patients receiving RT (n = 85) had worse baseline prognostic factors than patients without RT (n = 66). One-year overall survival (OS) was lower for RT patients than patients without RT (66%, 95% CI: 55-77% vs 83%, 95% CI: 73-92%). One-year OS was 61% for patients receiving RT before anti-PD-1 (95% CI: 46-76%), 78% for RT during anti-PD-1 (95% CI: 60-95%), and 58% for RT after anti-PD-1 (95% CI: 26-89%). On Cox regression, OS for patients without RT did not differ significantly from patients receiving RT during anti-PD-1 (HR 1.07, 95% CI: 0.41-2.84) or RT before anti-PD-1 (HR 0.56, 95% CI: 0.21-1.45). RT and anti-PD-1 therapy administered within 6 weeks of each other was well tolerated. CONCLUSION: RT can be safely administered with anti-PD-1 therapy. Despite worse baseline prognostic characteristics for patients receiving RT, OS was similar for patients receiving concurrent RT with anti-PD-1 therapy compared to patients receiving anti-PD-1 therapy alone.

Multireader Determination of Clinically Significant Obstruction Using Hyperpolarized 129Xe-Ventilation MRI.

OBJECTIVE: The objective of our study was to identify the magnitude and distribution of ventilation defect scores (VDSs) derived from hyperpolarized (HP) 129Xe-MRI associated with clinically relevant airway obstruction. MATERIALS AND METHODS: From 2012 to 2015, 76 subjects underwent HP 129Xe-MRI (48 healthy volunteers [mean age ± SD, 54 ± 17 years]; 20 patients with asthma [mean age, 44 ± 20 years]; eight patients with chronic obstructive pulmonary disease [mean age, 67 ± 5 years]). All subjects underwent spirometry 1 day before MRI to establish the presence of airway obstruction (forced expiratory volume in 1 second-to-forced vital capacity ratio [FEV1/FVC] < 70%). Five blinded readers assessed the degree of ventilation impairment and assigned a VDS (range, 0-100%). Interreader agreement was assessed using the Fleiss kappa statistic. Using FEV1/FVC as the reference standard, the optimum VDS threshold for the detection of airway obstruction was estimated using ROC curve analysis with 10-fold cross-validation. RESULTS: Compared with the VDSs in healthy subjects, VDSs in patients with airway obstruction were significantly higher (p < 0.0001) and significantly correlated with disease severity (r = 0.66, p < 0.0001). Ventilation defects in subjects with airway obstruction did not show a location-specific pattern (p = 0.158); however, defects in healthy control subjects were more prevalent in the upper lungs (p = 0.014). ROC curve analysis yielded an optimal threshold of 12.4% ± 6.1% (mean ± SD) for clinically significant VDS. Interreader agreement for 129Xe-MRI was substantial (κ = 0.71). CONCLUSION: This multireader study of a diverse cohort of patients and control subjects suggests a 129Xe-ventilation MRI VDS of 12.4% or greater represents clinically significant obstruction.

Negative Biopsy of Focal Hepatic Lesions: Decision Tree Model for Patient Management.

OBJECTIVE: The purpose of this study was to investigate patient- and procedure-related variables affecting the false-negative rate of ultrasound (US)-guided liver biopsy and to develop a standardized patient-tailored predictive model for the management of negative biopsy results. MATERIALS AND METHODS: We retrospectively included 389 patients (mean age ± SD, 62 ± 12 years old) who had undergone US-guided liver biopsy of 405 liver lesions between January 1, 2013, and June 30, 2015. We collected multiple patient- and procedure-related variables. By comparing pathology reports of biopsy and the reference standard (further histology or imaging follow-up), we were able to categorize the biopsy results as true-positive, true-negative, and false-negative. Diagnostic accuracy and diagnostic yield were measured. Univariate and multivariate analyses were performed to identify variables predicting false-negative results. A standardized patient-tailored predictive model of false-negative results based on a decision tree was fitted. RESULTS: Diagnostic accuracy and diagnostic yield were 93.8% (380/405) and 89.4% (362/405), respectively. The false-negative rate was 6.5% (25/387). Predictive variables of false-negative results at univariate analysis included body mass index, lesion size, sample acquisition techniques, and immediate specimen adequacy. The only independent predictors at multivariate analysis were patient age and Charlson comorbidity index. By combining lesion size and location with patient age and history of malignancy, we developed a decision tree model that predicts false-negative results with high confidence (up to 100%). CONCLUSION: False-negative results are not negligible at US-guided liver biopsy. The combination of selected lesion- and patient-specific variables may help predict when aggressive management is warranted in patients with likely false-negative results.