Louise M. Henderson

Utilization of Surveillance for Hepatocellular Carcinoma Among Hepatitis C Virus–Infected Veterans in the United States

BACKGROUND Surveillance for hepatocellular carcinoma (HCC) is recommended for patients with hepatitis C virus (HCV) infection and cirrhosis. However, whether surveillance is being done as recommended is unknown. OBJECTIVE To examine the prevalence and determinants of HCC surveillance among HCV-infected patients with cirrhosis in Veterans Affairs (VA) health care facilities in the United States. DESIGN Retrospective cohort study of HCV-infected patients using data obtained from the national VA Hepatitis C Clinical Case Registry. SETTING 128 VA medical centers. PATIENTS HCV-infected patients with cirrhosis diagnosed between fiscal years 1998 and 2005. MEASUREMENTS Abdominal ultrasonography and measurement of α-fetoprotein for HCC surveillance were identified from administrative data by using a previously validated algorithm. Patients were categorized as having routine (tests done during at least 2 consecutive years in the 4 years after cirrhosis diagnosis), inconsistent (at least 1 test, but not routine), or no surveillance in the 4 years after cirrhosis diagnosis. Predictors of surveillance were identified by using hierarchical random-effects regression. RESULTS 126 670 patients with HCV were identified; 13 002 (10.1%) had cirrhosis. Approximately 42.0% of patients with cirrhosis received 1 or more HCC surveillance tests within the first year after the cirrhosis index date; however, a decline in receipt of surveillance was observed in the following 2 to 4 years. Among patients with cirrhosis and at least 2 years of follow-up, routine surveillance occurred in 12.0%, inconsistent surveillance in 58.5%, and no surveillance in 29.5%. Lower medical and psychological comorbid conditions, presence of varices, and the absence of decompensated liver disease were associated with a higher likelihood of receiving routine surveillance. LIMITATIONS Hepatocellular carcinoma surveillance tests were indirectly identified from registry data. Physician recommendations could not be captured. CONCLUSION Few HCV-infected veterans with cirrhosis received routine HCC surveillance. New strategies are needed to improve the implementation of HCC surveillance in clinical practice. PRIMARY FUNDING SOURCE Houston Veterans Affairs Health Services Research and Development Center of Excellence and the National Cancer Institute.

Medication Usage and the Risk of Neoplasia in Patients with Barrett's Esophagus

BACKGROUND & AIMS Experimental evidence indicates that proton pump inhibitors (PPIs), nonsteroidal anti-inflammatory drugs (NSAIDs)/aspirin, and statins can protect patients with Barretts esophagus (BE) from developing neoplasias. However, only limited data are available on chemoprevention in patients with BE. METHODS A retrospective observational study was performed using data from patients with documented BE. Prescription information was collected from pharmacy records. Cox regression analyses were performed to examine the association between prescriptions for PPIs, NSAIDs/aspirin, or statins and the risk of developing esophageal dysplasia or adenocarcinoma during follow-up (from 1982 to 2005). RESULTS We examined 344 patients diagnosed with BE (mean age 61 years, 90.4% Caucasian, 94.2% male). After BE diagnosis, 67.2% of the patients were prescribed PPIs for a mean duration of 5.1 years; 49.1% were prescribed NSAIDs for a mean duration of 3.6 years, and 25.3% were prescribed statins for a mean duration of 2.8 years. During 2620 patient-years, high grade dysplasia or esophageal adenocarcinoma developed in 33 patients. PPI treatment after BE diagnosis was associated with a reduced risk of high grade dysplasia or cancer; this association persisted after adjustment for gender, age, and the length of BE. NSAID and/or aspirin therapy were associated with a nonsignificant trend toward lower incidence of high grade dysplasia or esophageal cancer. CONCLUSIONS PPI therapy reduces the risk of neoplasms in patients with BE. NSAIDs/aspirin appear to reduce cancer risk whereas statin use is not significantly associated with the risk of neoplasia in patients with BE.

Patterns of Breast Magnetic Resonance Imaging Use in Community Practice

IMPORTANCE Breast magnetic resonance imaging (MRI) is increasingly used for breast cancer screening, diagnostic evaluation, and surveillance. However, we lack data on national patterns of breast MRI use in community practice. OBJECTIVE To describe patterns of breast MRI use in US community practice during the period 2005 through 2009. DESIGN, SETTING, AND PARTICIPANTS Observational cohort study using data collected from 2005 through 2009 on breast MRI and mammography from 5 national Breast Cancer Surveillance Consortium registries. Data included 8931 breast MRI examinations and 1,288,924 screening mammograms from women aged 18 to 79 years. MAIN OUTCOMES AND MEASURES We calculated the rate of breast MRI examinations per 1000 women with breast imaging within the same year and described the clinical indications for the breast MRI examinations by year and age. We compared women screened with breast MRI to women screened with mammography alone for patient characteristics and lifetime breast cancer risk. RESULTS The overall rate of breast MRI from 2005 through 2009 nearly tripled from 4.2 to 11.5 examinations per 1000 women, with the most rapid increase from 2005 to 2007 (P = .02). The most common clinical indication was diagnostic evaluation (40.3%), followed by screening (31.7%). Compared with women who received screening mammography alone, women who underwent screening breast MRI were more likely to be younger than 50 years, white non-Hispanic, and nulliparous and to have a personal history of breast cancer, a family history of breast cancer, and extremely dense breast tissue (all P < .001). The proportion of women screened using breast MRI at high lifetime risk for breast cancer (>20%) increased during the study period from 9% in 2005 to 29% in 2009. CONCLUSIONS AND RELEVANCE Use of breast MRI for screening in high-risk women is increasing. However, our findings suggest that there is a need to improve appropriate use, including among women who may benefit from screening breast MRI.

National Performance Benchmarks for Modern Screening Digital Mammography: Update from the Breast Cancer Surveillance Consortium

Purpose To establish performance benchmarks for modern screening digital mammography and assess performance trends over time in U.S. community practice. Materials and Methods This HIPAA-compliant, institutional review board-approved study measured the performance of digital screening mammography interpreted by 359 radiologists across 95 facilities in six Breast Cancer Surveillance Consortium (BCSC) registries. The study included 1 682 504 digital screening mammograms performed between 2007 and 2013 in 792 808 women. Performance measures were calculated according to the American College of Radiology Breast Imaging Reporting and Data System, 5th edition, and were compared with published benchmarks by the BCSC, the National Mammography Database, and performance recommendations by expert opinion. Benchmarks were derived from the distribution of performance metrics across radiologists and were presented as 50th (median), 10th, 25th, 75th, and 90th percentiles, with graphic presentations using smoothed curves. Results Mean screening performance measures were as follows: abnormal interpretation rate (AIR), 11.6 (95% confidence interval [CI]: 11.5, 11.6); cancers detected per 1000 screens, or cancer detection rate (CDR), 5.1 (95% CI: 5.0, 5.2); sensitivity, 86.9% (95% CI: 86.3%, 87.6%); specificity, 88.9% (95% CI: 88.8%, 88.9%); false-negative rate per 1000 screens, 0.8 (95% CI: 0.7, 0.8); positive predictive value (PPV) 1, 4.4% (95% CI: 4.3%, 4.5%); PPV2, 25.6% (95% CI: 25.1%, 26.1%); PPV3, 28.6% (95% CI: 28.0%, 29.3%); cancers stage 0 or 1, 76.9%; minimal cancers, 57.7%; and node-negative invasive cancers, 79.4%. Recommended CDRs were achieved by 92.1% of radiologists in community practice, and 97.1% achieved recommended ranges for sensitivity. Only 59.0% of radiologists achieved recommended AIRs, and only 63.0% achieved recommended levels of specificity. Conclusion The majority of radiologists in the BCSC surpass cancer detection recommendations for screening mammography; however, AIRs continue to be higher than the recommended rate for almost half of radiologists interpreting screening mammograms.

Breast Tumor Prognostic Characteristics and Biennial vs Annual Mammography, Age, and Menopausal Status

IMPORTANCE Screening mammography intervals remain under debate in the United States. OBJECTIVE To compare the proportion of breast cancers with less vs more favorable prognostic characteristics in women screening annually vs biennially by age, menopausal status, and postmenopausal hormone therapy (HT) use. DESIGN, SETTING, AND PARTICIPANTS This was a study of a prospective cohort from 1996 to 2012 at Breast Cancer Surveillance Consortium facilities. A total of 15,440 women ages 40 to 85 years with breast cancer diagnosed within 1 year of an annual or within 2 years of a biennial screening mammogram. EXPOSURES We updated previous analyses by using narrower intervals for defining annual (11-14 months) and biennial (23-26 months) screening. MAIN OUTCOMES AND MEASURES We defined less favorable prognostic characteristics as tumors that were stage IIB or higher, size greater than 15 mm, positive nodes, and any 1 or more of these characteristics. We used log-binomial regression to model the proportion of breast cancers with less favorable characteristics following a biennial vs annual screen by 10-year age groups and by menopausal status and current postmenopausal HT use. RESULTS Among 15,440 women with breast cancer, most were 50 years or older (13,182 [85.4%]), white (12,063 [78.1%]), and postmenopausal (9823 [63.6%]). Among 2027 premenopausal women (13.1%), biennial screeners had higher proportions of tumors that were stage IIB or higher (relative risk [RR], 1.28 [95% CI, 1.01-1.63]; P=.04), size greater than 15 mm (RR, 1.21 [95% CI, 1.07-1.37]; P=.002), and with any less favorable prognostic characteristic (RR, 1.11 [95% CI, 1.00-1.22]; P=.047) compared with annual screeners. Among women currently taking postmenopausal HT, biennial screeners tended to have tumors with less favorable prognostic characteristics compared with annual screeners; however, 95% CIs were wide, and differences were not statistically significant (for stage 2B+, RR, 1.14 [95% CI, 0.89-1.47], P=.29; size>15 mm, RR, 1.13 [95% CI, 0.98-1.31], P=.09; node positive, RR, 1.18 [95% CI, 0.98-1.42], P=.09; any less favorable characteristic, RR, 1.12 [95% CI, 1.00-1.25], P=.053). The proportions of tumors with less favorable prognostic characteristics were not significantly larger for biennial vs annual screeners among postmenopausal women not taking HT (eg, any characteristic: RR, 1.03 [95% CI, 0.95-1.12]; P=.45), postmenopausal HT users after subdividing by type of hormone use (eg, any characteristic: estrogen+progestogen users, RR, 1.16 [95% CI, 0.91-1.47]; P=.22; estrogen-only users, RR, 1.14 [95% CI, 0.94-1.37]; P=.18), or any 10-year age group (eg, any characteristic: ages 40-49 years, RR, .1.04 [95% CI, 0.94-1.14]; P=.48; ages 50-59 years, RR, 1.03 [95% CI, 0.94-1.12]; P=.58; ages 60-69 years, RR, 1.07 [95% CI, 0.97-1.19]; P=.18; ages 70-85 years, RR, 1.05 [95% CI, 0.94-1.18]; P=.35). CONCLUSIONS AND RELEVANCE Premenopausal women diagnosed as having breast cancer following biennial vs annual screening mammography are more likely to have tumors with less favorable prognostic characteristics. Postmenopausal women not using HT who are diagnosed as having breast cancer following a biennial or annual screen have similar proportions of tumors with less favorable prognostic characteristics.

Barrett's esophagus in children and adolescents without neurodevelopmental or tracheoesophageal abnormalities: a prospective study

BACKGROUND Barretts esophagus (BE) in children has been examined in retrospective studies, consisting of case series and cross-sectional studies. OBJECTIVE To evaluate the prevalence and determinants of BE in children who are free from neurodevelopmental disorders and tracheoesophageal abnormalities. DESIGN A prospective, cross-sectional study. SETTING Three pediatric GI Centers in Houston, Texas; Phoenix, Arizona; and Portland, Maine between February 2006 and December 2007. PATIENTS This study involved children and adolescents consecutively presenting for elective upper endoscopy. Patients with neurodevelopmental and tracheoesophageal disorders were excluded. INTERVENTION Endoscopic pictures of all cases with suspected BE were independently reviewed and verified by two experienced investigators. Esophageal biopsy specimens were obtained in all patients, and targeted biopsy specimens also were obtained from suspected BE. MAIN OUTCOME MEASUREMENTS Endoscopically suspected BE and histologically confirmed BE. RESULTS A total of 840 patients (mean age 9.5 years) were enrolled and had complete questionnaire and endoscopic data. Twelve patients were suspected of having BE (prevalence of 1.43%; 95% confidence interval [CI], 0.73-2.45), and only 1 patient had intestinal metaplasia, for a prevalence of 0.12% (95% CI, 0-0.65), whereas the rest had gastric oxyntic glands (n=6) or squamous esophageal epithelium (n=5). Patients with suspected BE had a higher mean body mass index (23.0 vs 19.1, P=.05) and more chest pain (50% vs 13%, P<.01) than patients without BE or reflux esophagitis. There was a trend toward a higher frequency of dysphagia, heartburn, and regurgitation in patients with suspected BE. LIMITATIONS The accuracy of BE prevalence estimates is limited by the small number of cases. CONCLUSION BE is rare in children without neurodevelopmental delay or tracheoesophageal anomalies presenting for elective upper endoscopy.

Surveillance for Hepatocellular Carcinoma: Development and Validation of an Algorithm to Classify Tests in Administrative and Laboratory Data

BackgroundThe purpose of alpha-fetoprotein (AFP) and abdominal ultrasound (US) cannot be discerned in administrative data.AimWe developed an algorithm to identify AFP and US used as surveillance tests for hepatocellular carcinoma (HCC).MethodsWe evaluated 300 AFP and 301 US tests from a VA database. Surveillance predictors in the administrative files (diagnoses, labs) were examined in logistic regression models. We calculated model-based probabilities of HCC surveillance status, and developed classification procedures using single and multiple imputation methods.ResultsThe predictors of surveillance intent for AFP were absence of alcoholism, abdominal pain, ascites, diabetes and high AST levels. For US, the predictors of surveillance were prior AFP testing and HIV status and absence of abdominal pain, ascites, or drug dependence. For AFP classification, single imputation compared favorably with multiple imputation, both showing robustness in discrimination and calibration. For US both approaches were less robust in discrimination and calibration which was more moderate in multiple imputation than single imputation.ConclusionsPredictive algorithms in administrative files can be used to identify AFP performed for HCC surveillance, however, the intent of US is more difficult to identify.

Breast Cancer Characteristics Associated With Digital Versus Film-Screen Mammography for Screen-Detected and Interval Cancers

OBJECTIVE The purpose of this study was to determine whether pathologic findings of screen-detected and interval cancers differ for digital versus film mammography. MATERIALS AND METHODS Breast Cancer Surveillance Consortium data from 2003-2011 on 3,021,515 screening mammograms (40.3% digital, 59.7% film) of women 40-89 years old were reviewed. Cancers were considered screen detected if diagnosed within 12 months of an examination with positive findings and interval if diagnosed within 12 months of an examination with negative findings. Tumor characteristics for screen-detected and interval cancers were compared for digital versus film mammography by use of logistic regression models to estimate the odds ratio and 95% CI with adjustment for age, race and ethnicity, hormone therapy use, screening interval, examination year, and registry. Generalized estimating equations were used to account for correlation within facilities. RESULTS Among 15,729 breast cancers, 85.3% were screen detected and 14.7% were interval. Digital and film mammography had similar rates of screen-detected (4.47 vs 4.42 per 1000 examinations) and interval (0.73 vs 0.79 per 1000 examinations) cancers for digital versus film. In adjusted analyses, interval cancers diagnosed after digital examinations with negative findings were less likely to be American Joint Committee on Cancer stage IIB or higher (odds ratio, 0.69; 95% CI, 0.52-0.93), have positive nodal status (odds ratio, 0.78; 95% CI, 0.64-0.95), or be estrogen receptor negative (odds ratio, 0.71; 95% CI, 0.56-0.91) than were interval cancers diagnosed after a film examination with negative findings. CONCLUSION Screen-detected cancers diagnosed after digital and film mammography had similar rates of unfavorable tumor characteristics. Interval-detected cancers diagnosed after a digital examination were less likely to have unfavorable tumor features than those diagnosed after film mammography, but the absolute differences were small.

Five-Year Risk for Interval-Invasive Second Breast Cancer

BACKGROUND Earlier detection of second breast cancers after primary breast cancer (PBC) treatment improves survival, yet mammography is less accurate in women with prior breast cancer. The purpose of this study was to examine women presenting clinically with second breast cancers after negative surveillance mammography (interval cancers), and to estimate the five-year risk of interval-invasive second cancers for women with varying risk profiles. METHODS We evaluated a prospective cohort of 15 114 women with 47 717 surveillance mammograms diagnosed with stage 0-II unilateral PBC from 1996 through 2008 at facilities in the Breast Cancer Surveillance Consortium. We used discrete time survival models to estimate the association between odds of an interval-invasive second breast cancer and candidate predictors, including demographic, PBC, and imaging characteristics. All statistical tests were two-sided. RESULTS The cumulative incidence of second breast cancers after five years was 54.4 per 1000 women, with 325 surveillance-detected and 138 interval-invasive second breast cancers. The five-year risk of interval-invasive second cancer for women with referent category characteristics was 0.60%. For women with the most and least favorable profiles, the five-year risk ranged from 0.07% to 6.11%. Multivariable modeling identified grade II PBC (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.15 to 3.31), treatment with lumpectomy without radiation (OR = 3.27, 95% CI = 1.91 to 5.62), interval PBC presentation (OR = 2.01, 95% CI 1.28 to 3.16), and heterogeneously dense breasts on mammography (OR = 1.54, 95% CI = 1.01 to 2.36) as independent predictors of interval-invasive second breast cancers. CONCLUSIONS PBC diagnosis and treatment characteristics contribute to variation in subsequent-interval second breast cancer risk. Consideration of these factors may be useful in developing tailored post-treatment imaging surveillance plans.

Analyzing factors associated with women’s attitudes and behaviors toward screening mammography using design-based logistic regression

We examined the factors associated with screening mammography adherence behaviors and influencing factors on women’s attitudes toward mammography in non-adherent women. Design-based logistic regression models were developed to characterize the influencing factors, including socio-demographic, health related, behavioral characteristics, and knowledge of breast cancer/mammography, on women’s compliance with and attitudes toward mammography using the 2003 Health Information National Trends Survey data. Findings indicate significant associations among adherence to mammography and marital status, income, health coverage, being advised by a doctor to have a mammogram, having had Pap smear before, perception of chance of getting breast cancer, and knowledge of mammography (frequency of doing mammogram) in both women younger than 65 and women aged 65 and older. However, number of visits to a healthcare provider per year and lifetime number of smoked cigarettes are only significant for women younger than 65. Factors significantly associated with attitudes toward mammography in non-adherent women are age, being advised by a doctor to have a mammogram, and seeking cancer information. To enhance adherence to mammography programs, physicians need to continue to advise their patients to obtain mammograms. In addition, increasing women’s knowledge about the frequency and starting age for screening mammography may improve women’s adherence. Financially related factors such as income and insurance are also shown to be significant factors. Hence, healthcare policies aimed at providing breast cancer screening services to underserved women will likely enhance mammography participation.