Screening mammographic performance by race and age in the National Mammography Database: 29,479,665 screening mammograms from 13,181,241 women.

PURPOSE: There are insufficient large-scale studies comparing the performance of screening mammography in women of different races. This study aims to compare the screening performance metrics across racial and age groups in the National Mammography Database (NMD). METHODS: All screening mammograms performed between January 1, 2008, and December 31, 2021, in women aged 30-100 years from 746 mammography facilities in 46 U.S. states in the NMD were included. Patients were stratified by 10-year age intervals and 5 racial groups (African American, American Indian, Asian, White, unknown). Incidence of risk factors (breast density, personal history, family history of breast cancer, age), and time since prior exams were compared. Five screening mammography metrics were calculated: recall rate (RR), cancer detection rate (CDR), positive predictive values for recalls (PPV1), biopsy recommended (PPV2) and biopsy performed (PPV3). RESULTS: 29,479,655 screening mammograms performed in 13,181,241 women between January 1, 2008, and December 31, 2021, from the NMD were analyzed. The overall mean performance metrics were RR 10.00% (95% CI 9.99-10.02), CDR 4.18/1000 (4.16-4.21), PPV1 4.18% (4.16-4.20), PPV2 25.84% (25.72-25.97), PPV3 25.78% (25.66-25.91). With advancing age, RR significantly decreases, while CDR, PPV1, PPV2, and PPV3 significantly increase. Incidence of personal/family history of breast cancer, breast density, age, prior mammogram availability, and time since prior mammogram were mostly similar across all races. Compared to White women, African American women had significantly higher RR, but lower CDR, PPV1, PPV2 and PPV3. CONCLUSIONS: Benefits of screening mammography increase with age, including for women age > 70 and across all races. Screening mammography is effective; with lower RR and higher CDR, PPV2, and PPV3 with advancing age. African American women have poorer outcomes from screening mammography (higher RR and lower CDR), compared to White and all women in the NMD. Racial disparity can be partly explained by higher rate of African American women lost to follow up.

Rate and Timeliness of Diagnostic Evaluation and Biopsy After Recall From Screening Mammography in the National Mammography Database.

OBJECTIVE: To describe the rate and timeliness of diagnostic resolution after an abnormal screening mammogram in the ACR's National Mammography Database. METHODS: Abnormal screening mammograms (BI-RADS 0 assessment) in the National Mammography Database from January 1, 2008, to December 31, 2021, were retrospectively identified. The rates and timeliness of follow-up with diagnostic evaluation and biopsy were assessed and compared across patient and facility demographics. RESULTS: Among the 2,874,310 screening mammograms reported as abnormal, follow-up was documented in 66.4% (n = 1,909,326). Lower follow-up rates were observed in younger women (59.4% in women < 30 years, 63.2% in women 30-39 years), Black (57.4%) and American Indian (59.5%) women, and women with no breast cancer family history (63.0%). The overall median time to diagnostic evaluation was 9 days. Longer median diagnostic evaluation time was noted in Black (14 days), other or mixed race (14 days), and Hispanic women (13 days). Of the 318,977 recalled screening mammograms recommended for biopsy, 238,556 (74.8%) biopsies were documented. Lower biopsy rates were noted in older women (71.5% in women aged ≥80) and Black (71.5%) and American Indian (52.2%) women. The overall median time from diagnostic evaluation to biopsy was 21 days. Longer median biopsy time was noted in older (23 days aged ≥80), Black (25 days), mixed or other race (26 days), and Hispanic women (23 days), and rural (24 days) or community hospital affiliated facilities (22 days). DISCUSSION: There is variability in the rates and timeliness of diagnostic evaluation and biopsy in women with abnormal screening mammogram. Subsets of women and facilities could benefit from targeted interventions to promote timely diagnostic resolution and biopsy after an abnormal screening mammogram.

Outcomes From More Than 1 Million People Screened for Lung Cancer With Low-Dose CT Imaging.

BACKGROUND: Lung cancer screening (LCS) with low-dose CT (LDCT) imaging was recommended in 2013, making approximately 8 million Americans eligible for LCS. The demographic characteristics and outcomes of individuals screened in the United States have not been reported at the population level. RESEARCH QUESTION: What are the outcomes among people screened and entered in the American College of Radiology's Lung Cancer Screening Registry compared with those of trial participants? STUDY DESIGN AND METHODS: This was a cohort study of individuals undergoing baseline LDCT imaging for LCS between 2015 and 2019. Predictors of adherence to annual screening were computed. LDCT scan interpretations by Lung Imaging Reporting and Data System (Lung-RADS) score, cancer detection rates (CDRs), and stage at diagnosis were compared with National Lung Cancer Screening Trial data. RESULTS: Adherence was 22.3%, and predictors of poor adherence included current smoking status and Hispanic or Black race. On baseline screening, 83% of patients showed negative results and 17% showed positive screening results. The overall CDR was 0.56%. The percentage of people with cancer detected at baseline was higher in the positive Lung-RADS categories at 0.4% for Lung-RADS category 3, 2.6% for Lung-RADS category 4A, 11.1% for Lung-RADS category 4B, and 19.9% for Lung-RADS category 4X. The cancer stage distribution was similar to that observed in the National Lung Cancer Screening Trial, with 53.5% of patients receiving a diagnosis of stage I cancer and 14.3% with stage IV cancer. Underreporting into the registry may have occurred. INTERPRETATION: This study revealed both the positive aspects of CT scan screening for lung cancer and the challenges that remain. Findings on CT imaging were correlated accurately with lung cancer detection using the Lung-RADS system. A significant stage shift toward early-stage lung cancer was present. Adherence to LCS was poor and likely contributes to the lower than expected cancer detection rate, all of which will impact the outcomes of patients undergoing screening for lung cancer.

Characteristics of Persons Screened for Lung Cancer in the United States : A Cohort Study.

BACKGROUND: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) was recommended by the U.S. Preventive Services Task Force (USPSTF) in 2013, making approximately 8 million Americans eligible for screening. The demographic characteristics and adherence of persons screened in the United States have not been reported at the population level. OBJECTIVE: To define sociodemographic characteristics and adherence among persons screened and entered into the American College of Radiology's Lung Cancer Screening Registry (LCSR). DESIGN: Cohort study. SETTING: United States, 2015 to 2019. PARTICIPANTS: Persons receiving a baseline LDCT for LCS from 3625 facilities reporting to the LCSR. MEASUREMENTS: Age, sex, and smoking status distributions (percentages) were computed among persons who were screened and among respondents in the 2015 National Health Interview Survey (NHIS) who were eligible for screening. The prevalence between the LCSR and the NHIS was compared with prevalence ratios (PRs) and 95% CIs. Adherence to annual screening was defined as having a follow-up test within 11 to 15 months of an initial LDCT. RESULTS: Among 1 159 092 persons who were screened, 90.8% (n = 1 052 591) met the USPSTF eligibility criteria. Compared with adults from the NHIS who met the criteria (n = 1257), screening recipients in the LCSR were older (34.7% vs. 44.8% were aged 65 to 74 years; PR, 1.29 [95% CI, 1.20 to 1.39]), more likely to be female (41.8% vs. 48.1%; PR, 1.15 [CI, 1.08 to 1.23]), and more likely to currently smoke (52.3% vs. 61.4%; PR, 1.17 [CI, 1.11 to 1.23]). Only 22.3% had a repeated annual LDCT. If follow-up was extended to 24 months and more than 24 months, 34.3% and 40.3% were adherent, respectively. LIMITATIONS: Underreporting of LCS and missing data may skew demographic characteristics of persons reported to be screened. Underreporting of adherence may result in underestimates of follow-up. CONCLUSION: Approximately 91% of persons who had LCS met USPSTF eligibility criteria. In addition to continuing to target all eligible adults, men, those who formerly smoked, and younger eligible patients may be less likely to be screened. Adherence to annual follow-up screening was poor, potentially limiting screening effectiveness. PRIMARY FUNDING SOURCE: None.

Use of Screening CT Colonography by Age and Race: A Study of Potential Access Barriers Related to Medicare Noncoverage Based on Data From the ACR's National CT Colonography Registry.

OBJECTIVE: The primary objectives of this investigation were to evaluate the use of screening CT colonography (CTC) examinations by age comparing individuals of Medicare-eligible age to younger cohorts and to determine if the association between use of CTC and Medicare-eligible age varies by race. Although the Affordable Care Act requires commercial insurance coverage of screening CTC, Medicare does not cover screening CTC. MATERIALS AND METHODS: Using the ACR's CTC registry, the distribution of procedures by age was evaluated using a negative binomial model with patient age (to capture overall trend), indicator of Medicare-eligible age (to capture immediate changes in trend at age 65), and their interaction (to capture gradual changes after age 65) as independent variables. The association between the number of screening CTCs and age was compared by racial identity. RESULTS: The CTC registry contained data on 12,648 screening examinations. Between ages 52 and 64, the number of screening examinations increased; each additional age year was associated with a 5.3% (P < .001) increase in the number of screenings. However, after age 65, the number of screening examinations decreased by -6.9% per additional year of age above 65 compared with the trend between ages 52 and 64 (P < .001). The modal age group for CTC use was 65 to 69 years in white and 55 to 59 in black individuals. CONCLUSION: After age 65, the number of screening CTC examinations decreased, likely due, at least in part, to lack of Medicare coverage. Medicare noncoverage may have a disproportionate impact on black patients and other racial minorities.

Obesity in adults with epilepsy.

Sixty-eight percent of the US adult population is overweight, and 35% is obese. The rate of obesity in patients with epilepsy is unknown. Its determination was the goal of the present study. Weight and height were measured, and body mass index (BMI) was calculated in all newly evaluated patients with epilepsy at a single epilepsy center between 2003 and 2009. Five hundred fifty-four patients aged ≥16-87years were included (62.7% were women, 12.6% with primary generalized epilepsy, and 86.4% with localization-related epilepsy). Three hundred six (55.2%) patients were overweight or obese (BMI>25kg/m(2)) (95% confidence interval [CI]: 51.1%-59.3%), 173 (31.2%) were obese (BMI>30kg/m(2)) (95% CI: 27.5%-35.2%), and 24 (4.3%) were morbidly obese (BMI>40kg/m(2)). Overweight/obesity combined was more common in men (65.4% [95% CI: 58.8%-71.5%]) than in women (49% women [95% CI: 43.3%-54.3%]) (p≤0.001). The rate of overweight/obesity combined trended to be greater in blacks (67.9%) than in whites (51.9%). Obesity alone was more common in blacks (46.4%) than in whites (29.4%), with too few Hispanics and Asians to allow a comparison. Overweight/obesity and obesity rates were higher in patients with refractory than nonrefractory epilepsy (60.4% vs. 49.2% overweight, 36.9% vs.24.6% obesity). Obesity was more common in patients treated with polytherapy than those treated with monotherapy (37.7% vs. 25%). There were no associations between obesity and other disease characteristics such as epilepsy type, duration, or etiology. Obesity is common in patients with epilepsy, similar to the general population.

GSTM1, GSTT1 null variants, and GPX1 single nucleotide polymorphism are not associated with bladder cancer risk in Egypt.

BACKGROUND: Bladder cancer is the most common male malignancy in Egypt, consists predominantly of urothelial cell carcinoma (UCC) and squamous cell carcinoma (SCC), and disparities in incidence exist between men and women regardless of geographic region. Tobacco smoke exposure and Schistosoma haematobium (SH) infection and the presence of GSTM1, GSTT1, and GPX1 genotypes, as modulators of the carcinogenic effect of reactive oxidative species, were hypothesized to modify bladder cancer risk and possibly explain these gender differences. METHODS: We evaluated the association between bladder cancer risk and functional polymorphisms in the GSTM1, GSTT1, and GPX1 genes in 625 cases and 626 matched population-based controls in Egypt and assessed for potential interactions between these candidate genes and environmental exposures, such as smoking and SH infection. We analyzed the risk for developing UCC and SCC separately. RESULTS: None of these functional polymorphisms were significantly associated with bladder cancer risk. There were no significant interactions between genotypes and smoking or SH infection in this population, nor was any difference detected in genotypic risk between men and women. CONCLUSIONS: Our findings suggest that common genetic variations in GSTM1, GSTT1, and GPX1 are not associated with bladder cancer risk overall and that well-known environmental risk factors, such as smoking and SH infection, do not interact with these genes to modulate the risk. IMPACT: Our data indicate that common genetic variations in GSTM1, GSTT1, and GPX1 were not associated with bladder cancer risk.

Urinary estrogen metabolites and prostate cancer risk: a pilot study.

BACKGROUND: The high incidence of and few identified risk factors for prostate cancer underscore the need to further evaluate markers of prostate carcinogenesis. The aim of this pilot study was to evaluate urinary estrogen metabolites as a biomarker of prostate cancer risk. METHODS: Using a liquid chromatography-tandem mass spectrometry method, urinary concentrations of 15 estrogen metabolites were determined in 77 prostate cancer cases, 77 healthy controls, and 37 subjects who had no evidence of prostate cancer after a prostate biopsy. RESULTS: We observed an inverse association between the urinary 16-ketoestradiol (16-KE2) and 17-epiestriol (17-epiE3)--metabolites with high estrogenic activity--and prostate cancer risk. Men in the lowest quartile of 16-KE2, had a 4.6-fold risk of prostate cancer (OR=4.62, 95% CI=1.34-15.99), compared with those in the highest quartile. CONCLUSIONS: We observed modest differences in estrogen metabolite concentrations between prostate cancer patients and subjects without cancer. Larger studies with both androgen and estrogen measurements are needed to confirm these results to clarify further whether estrogen metabolites are independent biomarkers for prostate cancer risk and whether androgen/estrogen imbalance influences prostate cancer risk.

Viral and non-viral risk factors for non-Hodgkin's lymphoma in Egypt: heterogeneity by histological and immunological subtypes.

OBJECTIVE: Non-Hodgkin's lymphomas (NHL) are etiologically heterogeneous malignancies. In Egypt, we previously reported an association of increased NHL risk with chronic hepatitis C virus (HCV) infection. Our present aim is to assess the association between HCV infection and histological subtypes of NHL. METHODS: We conducted a case-control study at the National Cancer Institute of Cairo University. Cases with NHL (n = 486) were matched to controls (n = 786) who were orthopedic patients from the same referral regions. Participants provided a blood sample for HCV markers (anti-HCV, HCV RNA) and answered a questionnaire on possible risk factors. Case-control differences were assessed by odds ratios and 95% confidence intervals from logistic regression analysis. RESULTS: Cases with diffuse large B cell lymphoma (n = 146), chronic lymphocytic leukemia (n = 58), marginal zone lymphoma (n = 24), follicular lymphoma (n = 23), and mantle cell lymphoma (n = 16) were recruited. HCV RNA prevalence was 27% in controls and 26%-48% in the NHL subgroups: it was associated (p < 0.001) with diffuse large B cell, marginal zone, and follicular lymphomas with odds ratios of 3.2, 4.4, and 3.3, respectively. CONCLUSION: HCV is a risk factor for diffuse large B cell, marginal zone, and follicular lymphomas in Egypt.

Detection of hepatocellular carcinoma using glycomic analysis.

PURPOSE: Hepatocellular carcinoma (HCC) represents an increasing health problem in the United States. Serum alpha-fetoprotein, the currently used clinical marker, is elevated in only approximately 60% of HCC patients; therefore, the identification of additional markers is expected to have significant public health impact. The objective of our study was to quantitatively assess N-glycans originating from serum glycoproteins as alternative markers for the detection of HCC. EXPERIMENTAL DESIGN: We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for quantitative comparison of 83 N-glycans in serum samples of 202 participants (73 HCC cases, 77 age- and gender-matched cancer-free controls, and 52 patients with chronic liver disease). N-glycans were enzymatically released from serum glycoproteins and permethylated before mass spectrometric quantification. RESULTS: The abundance of 57 N-glycans was significantly altered in HCC patients compared with controls. The sensitivity of six individual glycans evaluated for separation of HCC cases from population controls ranged from 73% to 90%, and the specificity ranged from 36% to 91%. A combination of three selected N-glycans was sufficient to classify HCC with 90% sensitivity and 89% specificity in an independent validation set of patients with chronic liver disease. The three N-glycans remained associated with HCC after adjustment for chronic viral infection and other known covariates, whereas the other glycans increased significantly at earlier stages of the progression of chronic viral infection to HCC. CONCLUSION: A set of three identified N-glycans is sufficient for the detection of HCC with 90% prediction accuracy in a population with high rates of hepatitis C viral infection. Further evaluation of a wider clinical utility of these candidate markers is warranted.

Analysis of MALDI-TOF mass spectrometry data for discovery of peptide and glycan biomarkers of hepatocellular carcinoma.

This paper presents computational methods to analyze MALDI-TOF mass spectrometry data for quantitative comparison of peptides and glycans in serum. The methods are applied to identify candidate biomarkers in serum samples of 203 participants from Egypt; 73 hepatocellular carcinoma (HCC) cases, 52 patients with chronic liver disease (CLD) consisting of cirrhosis and fibrosis cases, and 78 population controls. Two complementary sample preparation methods were applied prior to generating mass spectra: (1) low molecular weight (LMW) enrichment of each serum sample was carried out for MALDI-TOF quantification of peptides, and (2) glycans were enzymatically released from proteins in each serum sample and permethylated for MALDI-TOF quantification of glycans. A peak selection algorithm was applied to identify the most useful peptide and glycan peaks for accurate detection of HCC cases from high-risk population of patients with CLD. In addition to global peaks selected by the whole population based approach, where identically labeled patients are treated as a single group, subgroup-specific peaks were identified by searching for peaks that are differentially abundant in a subgroup of patients only. The peak selection process was preceded by peak screening, where we eliminated peaks that have significant association with covariates such as age, gender, and viral infection based on the peptide and glycan spectra from population controls. The performance of the selected peptide and glycan peaks was evaluated in terms of their ability in detecting HCC cases from patients with CLD in a blinded validation set and through the cross-validation method. Finally, we investigated the possibility of using both peptides and glycans in a panel to enhance the diagnostic capability of these candidate markers. Further evaluation is needed to examine the potential clinical utility of the candidate peptide and glycan markers identified in this study.

Analysis of MALDI-TOF mass spectrometry data for detection of glycan biomarkers.

We present a computational framework for analysis of MALDI-TOF mass spectrometry data to enable quantitative comparison of glycans in serum. The proposed framework enables a systematic selection of glycan structures that have good generalization capability in distinguishing subjects from two pre-labeled groups. We applied the proposed method for a biomarker discovery study that involves 203 participants from Cairo, Egypt; 73 hepatocellular carcinoma (HCC) cases, 52 patients with chronic liver disease (CLD), and 78 healthy individuals. Glycans were enzymatically released from proteins in serum and permethylated prior to mass spectrometric quantification. A subset of the participants (35 HCC and 35 CLD cases) was used as a training set to select global and subgroup-specific peaks. The peak selection step is preceded by peak screening, where we eliminate peaks that seem to have association with covariates such as age, gender, and viral infection based on the 78 spectra from healthy individuals. To ensure that the global peaks have good generalization capability, we subjected the entire spectral preprocessing and peak selection step to a cross-validation; a randomly selected subset of the training set was used for spectral preprocessing and peak selection in multiple runs with resubstitution. In addition to global peak identification method, we describe a new approach that allows the selection of subgroup-specific glycans by searching for glycans that display differential abundance in a subgroup of patients only. The performance of the global and subgroup-specific peaks is evaluated via a blinded independent set that comprises of 38 HCC and 17 CLD cases. Further evaluation of the potential clinical utility of the selected global and subgroup-specific candidate markers is needed.

Integrated peptide and glycan biomarker discovery using MALDI-TOF mass spectrometry.

Quantitative comparison of peptides and glycans in serum is conducted using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) to identify biomarkers. A peak selection algorithm is developed to identify a panel of integrated peptide and glycan peaks to distinguish hepatocellular carcinoma (HCC) cases from high-risk population of patients with chronic liver disease (CLD). Candidate peptide and glycan markers selected frequently in multiple runs of the algorithm are presented. The performance of these markers is evaluated in terms of their ability to distinguish HCC cases from patients with CLD in a blinded validation set.

Candidate markers for the detection of hepatocellular carcinoma in low-molecular weight fraction of serum.

Hepatocellular carcinoma (HCC) represents an important public health problem in Egypt where up to 90% of HCC cases are attributable to hepatitis C viral (HCV) infection. Serum alpha-fetoprotein is elevated in only approximately 60% of HCC patients. The development of effective markers for the detection of HCC could have an impact on cancer mortality and significant public health implications worldwide. The objective of our study was to assess six candidate markers for detection of HCC identified by mass spectrometric analysis of enriched serum. The study examined 78 HCC cases and 72 age- and gender-matched cancer-free controls recruited from the Egyptian population. Matrix-assisted laser desorption-ionization time-of-flight mass spectrometric analysis of enriched low-molecular weight fraction of serum was used for identification of the candidate markers. Our analyses show that all six candidate markers are associated with HCC after adjustment for important covariates including HCV and hepatitis B viral infections. The marker candidates are independently predictive of HCC with areas under the receiver operating characteristic (AuROC) curve ranging from 63-93%. A combination of the six markers improves prediction accuracy to 100% sensitivity, 91% specificity and 98% AuROC curve in an independent test set of 50 patients. Two of the candidate markers were identified by sequencing as fragments of complement C3 and C4. In conclusion, a set of six peptides distinguished with high prediction accuracy HCC from controls in an Egyptian population with a high rate of chronic HCV infection. Further evaluation of these marker candidates for the diagnosis of HCC is needed.

Analysis of mass spectral serum profiles for biomarker selection.

MOTIVATION: Mass spectrometric profiles of peptides and proteins obtained by current technologies are characterized by complex spectra, high dimensionality and substantial noise. These characteristics generate challenges in the discovery of proteins and protein-profiles that distinguish disease states, e.g. cancer patients from healthy individuals. We present low-level methods for the processing of mass spectral data and a machine learning method that combines support vector machines, with particle swarm optimization for biomarker selection. RESULTS: The proposed method identified mass points that achieved high prediction accuracy in distinguishing liver cancer patients from healthy individuals in SELDI-QqTOF profiles of serum. AVAILABILITY: MATLAB scripts to implement the methods described in this paper are available from the HWR's lab website http://lombardi.georgetown.edu/labpage