Search

BackgroundExamining screening outcomes by breast density for breast magnetic resonance imaging (MRI) with or without mammography could inform discussions about supplemental MRI in women with dense breasts.MethodsWe evaluated 52 237 women aged 40-79 years who underwent 2611 screening MRIs alone and 6518 supplemental MRI plus mammography pairs propensity score-matched to 65 810 screening mammograms. Rates per 1000 examinations of interval, advanced, and screen-detected early stage invasive cancers and false-positive recall and biopsy recommendation were estimated by breast density (nondense = almost entirely fatty or scattered fibroglandular densities; dense = heterogeneously/extremely dense) adjusting for registry, examination year, age, race and ethnicity, family history of breast cancer, and prior breast biopsy.ResultsScreen-detected early stage cancer rates were statistically higher for MRI plus mammography vs mammography for nondense (9.3 vs 2.9; difference = 6.4, 95% confidence interval [CI] = 2.5 to 10.3) and dense (7.5 vs 3.5; difference = 4.0, 95% CI = 1.4 to 6.7) breasts and for MRI vs MRI plus mammography for dense breasts (19.2 vs 7.5; difference = 11.7, 95% CI = 4.6 to 18.8). Interval rates were not statistically different for MRI plus mammography vs mammography for nondense (0.8 vs 0.5; difference = 0.4, 95% CI = -0.8 to 1.6) or dense breasts (1.5 vs 1.4; difference = 0.0, 95% CI = -1.2 to 1.3), nor were advanced cancer rates. Interval rates were not statistically different for MRI vs MRI plus mammography for nondense (2.6 vs 0.8; difference = 1.8 (95% CI = -2.0 to 5.5) or dense breasts (0.6 vs 1.5; difference = -0.9, 95% CI = -2.5 to 0.7), nor were advanced cancer rates. False-positive recall and biopsy recommendation rates were statistically higher for MRI groups than mammography alone.ConclusionMRI screening with or without mammography increased rates of screen-detected early stage cancer and false-positives for women with dense breasts without a concomitant decrease in advanced or interval cancers.

BackgroundThere are no consensus guidelines for supplemental breast cancer screening with whole-breast ultrasound. However, criteria for women at high risk of mammography screening failures (interval invasive cancer or advanced cancer) have been identified. Mammography screening failure risk was evaluated among women undergoing supplemental ultrasound screening in clinical practice compared with women undergoing mammography alone.MethodsA total of 38,166 screening ultrasounds and 825,360 screening mammograms without supplemental screening were identified during 2014-2020 within three Breast Cancer Surveillance Consortium (BCSC) registries. Risk of interval invasive cancer and advanced cancer were determined using BCSC prediction models. High interval invasive breast cancer risk was defined as heterogeneously dense breasts and BCSC 5-year breast cancer risk ≥2.5% or extremely dense breasts and BCSC 5-year breast cancer risk ≥1.67%. Intermediate/high advanced cancer risk was defined as BCSC 6-year advanced breast cancer risk ≥0.38%.ResultsA total of 95.3% of 38,166 ultrasounds were among women with heterogeneously or extremely dense breasts, compared with 41.8% of 825,360 screening mammograms without supplemental screening (p

ObjectiveWhen multiple surveillance mammograms are performed within an annual interval, the current guidance for one-year follow-up to determine breast cancer status results in shared follow-up periods in which a single breast cancer diagnosis can be attributed to multiple preceding examinations, posing a challenge for standardized performance assessment. We assessed the impact of using follow-up periods that eliminate the artifactual inflation of second breast cancer diagnoses.Materials and methodsWe evaluated surveillance mammograms from 2007-2016 in women with treated breast cancer linked with tumor registry and pathology outcomes. Second breast cancers included ductal carcinoma in situ or invasive breast cancer diagnosed during one-year follow-up. The cancer detection rate, interval cancer rate, sensitivity, and specificity were compared using different follow-up periods: standard one-year follow-up per the American College of Radiology versus follow-up that was shortened at the next surveillance mammogram if less than one year (truncated follow-up). Performance measures were calculated overall and by indication (screening, evaluation for breast problem, and short interval follow-up).ResultsOf 117971 surveillance mammograms, 20% (n = 23533) were followed by another surveillance mammogram within one year. Standard follow-up identified 1597 mammograms that were associated with second breast cancers. With truncated follow-up, the breast cancer status of 179 mammograms (11.2%) was revised, resulting in 1418 mammograms associated with unique second breast cancers. The interval cancer rate decreased with truncated versus standard follow-up (3.6 versus 4.9 per 1000 mammograms, respectively), with a difference (95% confidence interval [CI]) of -1.3 (-1.6, -1.1). The overall sensitivity increased to 70.4% from 63.7%, for the truncated versus standard follow-up, with a difference (95% CI) of 6.6% (5.6%, 7.7%). The specificity remained stable at 98.1%.ConclusionTruncated follow-up, if less than one year to the next surveillance mammogram, enabled second breast cancers to be associated with a single preceding mammogram and resulted in more accurate estimates of diagnostic performance for national benchmarks.

PurposeThe Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal and/or childhood medical imaging and subsequent cancer risk. This manuscript describes the study cohorts and research methods.MethodsThe RIC Study is a longitudinal study of children in two retrospective cohorts from 6 U.S. healthcare systems and from Ontario, Canada over the period 1995-2017. The fetal-exposure cohort includes children whose mothers were enrolled in the healthcare system during their entire pregnancy and followed to age 20. The childhood-exposure cohort includes children born into the system and followed while continuously enrolled. Imaging utilization was determined using administrative data. Computed tomography (CT) parameters were collected to estimate individualized patient organ dosimetry. Organ dose libraries for average exposures were constructed for radiography, fluoroscopy, and angiography, while diagnostic radiopharmaceutical biokinetic models were applied to estimate organ doses received in nuclear medicine procedures. Cancers were ascertained from local and state/provincial cancer registry linkages.ResultsThe fetal-exposure cohort includes 3,474,000 children among whom 6,606 cancers (2394 leukemias) were diagnosed over 37,659,582 person-years; 0.5% had in utero exposure to CT, 4.0% radiography, 0.5% fluoroscopy, 0.04% angiography, 0.2% nuclear medicine. The childhood-exposure cohort includes 3,724,632 children in whom 6,358 cancers (2,372 leukemias) were diagnosed over 36,190,027 person-years; 5.9% were exposed to CT, 61.1% radiography, 6.0% fluoroscopy, 0.4% angiography, 1.5% nuclear medicine.ConclusionThe RIC Study is poised to be the largest study addressing risk of childhood and adolescent cancer associated with ionizing radiation from medical imaging, estimated with individualized patient organ dosimetry.

Background The COVID-19 pandemic reduced mammography use, potentially delaying breast cancer diagnoses. Purpose To examine breast biopsy recommendations and breast cancers diagnosed before and during the COVID-19 pandemic by mode of detection (screen detected vs symptomatic) and women's characteristics. Materials and Methods In this secondary analysis of prospectively collected data, monthly breast biopsy recommendations after mammography, US, or both with subsequent biopsy performed were examined from 66 facilities of the Breast Cancer Surveillance Consortium between January 2019 and September 2020. The number of monthly and cumulative biopsies recommended and performed and the number of subsequent cancers diagnosed during the pandemic period (March 2020 to September 2020) were compared with data from the prepandemic period using Wald χ2 tests. Analyses were stratified by mode of detection and race or ethnicity. Results From January 2019 to September 2020, 17 728 biopsies were recommended and performed, with 6009 cancers diagnosed. From March to September 2020, there were substantially fewer breast biopsy recommendations with cancer diagnoses when compared with the same period in 2019 (1650 recommendations in 2020 vs 2171 recommendations in 2019 [24% fewer], P < .001), predominantly due to fewer screen-detected cancers (722 cancers in 2020 vs 1169 cancers in 2019 [38% fewer], P < .001) versus symptomatic cancers (895 cancers in 2020 vs 965 cancers in 2019 [7% fewer], P = .27). The decrease in cancer diagnoses was largest in Asian (67 diagnoses in 2020 vs 142 diagnoses in 2019 [53% fewer], P = .06) and Hispanic (82 diagnoses in 2020 vs 145 diagnoses in 2019 [43% fewer], P = .13) women, followed by Black women (210 diagnoses in 2020 vs 287 diagnoses in 2019 [27% fewer], P = .21). The decrease was smallest in non-Hispanic White women (1128 diagnoses in 2020 vs 1357 diagnoses in 2019 [17% fewer], P = .09). Conclusion There were substantially fewer breast biopsies with cancer diagnoses during the COVID-19 pandemic from March to September 2020 compared with the same period in 2019, with Asian and Hispanic women experiencing the largest declines, followed by Black women. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Heller in this issue.

BackgroundEarly initiation of breast cancer screening is recommended for high-risk women, including survivors of childhood cancer treated with chest radiation. Recent studies suggest that female survivors of childhood leukemia or sarcoma treated without chest radiation are also at elevated early onset breast cancer risk. However, the potential clinical benefits and cost-effectiveness of early breast cancer screening among these women are uncertain.MethodsUsing data from the Childhood Cancer Survivor Study, we adapted 2 Cancer Intervention and Surveillance Modeling Network simulation models to reflect the elevated risks of breast cancer and competing mortality among leukemia and sarcoma survivors. Costs and utility weights were based on published studies and databases. Outcomes included breast cancer deaths averted, false-positive screening results, benign biopsies, and incremental cost-effectiveness ratios.ResultsIn the absence of screening, the lifetime risk of dying from breast cancer among survivors was 6.8% to 7.0% across models. Early initiation of annual mammography with breast magnetic resonance imaging screening between ages 25 and 40 years would avert 52.6% to 64.3% of breast cancer deaths. When costs and quality-of-life impacts were considered, screening starting at age 40 years was the only strategy with an incremental cost-effectiveness ratio below the $100 000 per quality-adjusted life-year (QALY) gained cost-effectiveness threshold ($27 680 to $44 380 per QALY gained across models).ConclusionsAmong survivors of childhood leukemia or sarcoma, early initiation of breast cancer screening at age 40 years may reduce breast cancer deaths by half and is cost-effective. These findings could help inform screening guidelines for survivors treated without chest radiation.

BackgroundTo facilitate community-based epidemiologic studies of pediatric leukemia, we validated use of ICD-9-CM diagnosis codes to identify pediatric leukemia cases in electronic medical records of six U.S. integrated health plans from 1996-2015 and evaluated the additional contributions of procedure codes for diagnosis/treatment.ProceduresSubjects (N = 408) were children and adolescents born in the health systems and enrolled for at least 120 days after the date of the first leukemia ICD-9-CM code or tumor registry diagnosis. The gold standard was the health system tumor registry and/or medical record review. We calculated positive predictive value (PPV) and sensitivity by number of ICD-9-CM codes received in the 120-day period following and including the first code. We evaluated whether adding chemotherapy and/or bone marrow biopsy/aspiration procedure codes improved PPV and/or sensitivity.ResultsRequiring receipt of one or more codes resulted in 99% sensitivity (95% confidence interval [CI]: 98-100%) but poor PPV (70%; 95% CI: 66-75%). Receipt of two or more codes improved PPV to 90% (95% CI: 86-93%) with 96% sensitivity (95% CI: 93-98%). Requiring at least four codes maximized PPV (95%; 95% CI: 92-98%) without sacrificing sensitivity (93%; 95% CI: 89-95%). Across health plans, PPV for four codes ranged from 84-100% and sensitivity ranged from 83-95%. Including at least one code for a bone marrow procedure or chemotherapy treatment had minimal impact on PPV or sensitivity.ConclusionsThe use of diagnosis codes from the electronic health record has high PPV and sensitivity for identifying leukemia in children and adolescents if more than one code is required.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has disrupted breast cancer control through short-term declines in screening and delays in diagnosis and treatments. We projected the impact of COVID-19 on future breast cancer mortality between 2020 and 2030.MethodsThree established Cancer Intervention and Surveillance Modeling Network breast cancer models modeled reductions in mammography screening use, delays in symptomatic cancer diagnosis, and reduced use of chemotherapy for women with early-stage disease for the first 6 months of the pandemic with return to prepandemic patterns after that time. Sensitivity analyses were performed to determine the effect of key model parameters, including the duration of the pandemic impact.ResultsBy 2030, the models project 950 (model range = 860-1297) cumulative excess breast cancer deaths related to reduced screening, 1314 (model range = 266-1325) associated with delayed diagnosis of symptomatic cases, and 151 (model range = 146-207) associated with reduced chemotherapy use in women with hormone positive, early-stage cancer. Jointly, 2487 (model range = 1713-2575) excess breast cancer deaths were estimated, representing a 0.52% (model range = 0.36%-0.56%) cumulative increase over breast cancer deaths expected by 2030 in the absence of the pandemic's disruptions. Sensitivity analyses indicated that the breast cancer mortality impact would be approximately double if the modeled pandemic effects on screening, symptomatic diagnosis, and chemotherapy extended for 12 months.ConclusionsInitial pandemic-related disruptions in breast cancer care will have a small long-term cumulative impact on breast cancer mortality. Continued efforts to ensure prompt return to screening and minimize delays in evaluation of symptomatic women can largely mitigate the effects of the initial pandemic-associated disruptions.

Background The COVID-19 pandemic reduced mammography utilization, potentially delaying breast cancer diagnoses. Purpose To examine breast biopsy recommendations and breast cancers diagnosed before and during the COVID-19 pandemic by mode of detection (screen-detected versus symptomatic) and women's characteristics. Materials and Methods In this secondary analysis of prospectively collected data, monthly breast biopsy recommendations following mammography and/or ultrasound with subsequent biopsy performed were examined from 66 facilities of the Breast Cancer Surveillance Consortium between January 2019 and September 2020. Monthly and cumulative biopsies recommended and performed, and subsequent cancers diagnosed in the pandemic period (March-September 2020) versus the pre-pandemic period were compared using Wald chi-squared tests. Analyses were stratified by mode of detection and race/ethnicity. Results From January 2019 to September 2020, 17,728 biopsies were recommended and performed with 6,009 subsequent cancers diagnosed. From March to September 2020, there were substantially fewer breast biopsy recommendations with cancer diagnoses compared to 2019 (1,650 in 2020 versus 2,171 in 2019, or 24% fewer in 2020; p

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic led to a near-total cessation of mammography services in the United States in mid-March 2020. It is unclear if screening and diagnostic mammography volumes have recovered to prepandemic levels and whether use has varied by women's characteristics.MethodsWe collected data on 461 083 screening mammograms and 112 207 diagnostic mammograms conducted during January 2019 through July 2020 at 62 radiology facilities in the Breast Cancer Surveillance Consortium. We compared monthly screening and diagnostic mammography volumes before and during the pandemic stratified by age, race and ethnicity, breast density, and family history of breast cancer.ResultsScreening and diagnostic mammography volumes in April 2020 were 1.1% (95% confidence interval [CI] = 0.5% to 2.4%) and 21.4% (95% CI = 18.7% to 24.4%) of the April 2019 prepandemic volumes, respectively, but by July 2020 had rebounded to 89.7% (95% CI = 79.6% to 101.1%) and 101.6% (95% CI = 93.8% to 110.1%) of the July 2019 prepandemic volumes, respectively. The year-to-date cumulative volume of screening and diagnostic mammograms performed through July 2020 was 66.2% (95% CI = 60.3% to 72.6%) and 79.9% (95% CI = 75.4% to 84.6%), respectively, of year-to-date volume through July 2019. Screening mammography rebound was similar across age groups and by family history of breast cancer. Monthly screening mammography volume in July 2020 for Black, White, Hispanic, and Asian women reached 96.7% (95% CI = 88.1% to 106.1%), 92.9% (95% CI = 82.9% to 104.0%), 72.7% (95% CI = 56.5% to 93.6%), and 51.3% (95% CI = 39.7% to 66.2%) of the July 2019 prepandemic volume, respectively.ConclusionsDespite a strong overall rebound in mammography volume by July 2020, the rebound lagged among Asian and Hispanic women, and a substantial cumulative deficit in missed mammograms accumulated, which may have important health consequences.

BackgroundA paucity of research addresses breast cancer screening strategies for women at lower-than-average breast cancer risk. The aim of this study was to examine screening harms and benefits among women aged 50-74 years at lower-than-average breast cancer risk by breast density.MethodsThree well-established, validated Cancer Intervention and Surveillance Network models were used to estimate the lifetime benefits and harms of different screening scenarios, varying by screening interval (biennial, triennial). Breast cancer deaths averted, life-years and quality-adjusted life-years gained, false-positives, benign biopsies, and overdiagnosis were assessed by relative risk (RR) level (0.6, 0.7, 0.85, 1 [average risk]) and breast density category, for US women born in 1970.ResultsScreening benefits decreased proportionally with decreasing risk and with lower breast density. False-positives, unnecessary biopsies, and the percentage overdiagnosis also varied substantially by breast density category; false-positives and unnecessary biopsies were highest in the heterogeneously dense category. For women with fatty or scattered fibroglandular breast density and a relative risk of no more than 0.85, the additional deaths averted and life-years gained were small with biennial vs triennial screening. For these groups, undergoing 4 additional screens (screening biennially [13 screens] vs triennially [9 screens]) averted no more than 1 additional breast cancer death and gained no more than 16 life-years and no more than 10 quality-adjusted life-years per 1000 women but resulted in up to 232 more false-positives per 1000 women.ConclusionTriennial screening from age 50 to 74 years may be a reasonable screening strategy for women with lower-than-average breast cancer risk and fatty or scattered fibroglandular breast density.

Background Since 2007, digital mammography and digital breast tomosynthesis (DBT) replaced screen-film mammography. Whether these technologic advances have improved diagnostic performance has, to the knowledge of the authors, not yet been established. Purpose To evaluate the performance and outcomes of surveillance mammography (digital mammography and DBT) performed from 2007 to 2016 in women with a personal history of breast cancer and compare with data from 1996 to 2007 and the performance of digital mammography screening benchmarks. Materials and Methods In this observational cohort study, five Breast Cancer Surveillance Consortium registries provided prospectively collected mammography data linked with tumor registry and pathologic outcomes. This study identified asymptomatic women with American Joint Committee on Cancer anatomic stages 0-III primary breast cancer who underwent surveillance mammography from 2007 to 2016. The primary outcome was a second breast cancer diagnosis within 1 year of mammography. Performance measures included the recall rate, cancer detection rate, interval cancer rate, positive predictive value of biopsy recommendation, sensitivity, and specificity. Results Among 32 331 women who underwent 117 971 surveillance mammographic examinations (112 269 digital mammographic examinations and 5702 DBT examinations), the mean age at initial diagnosis was 59 years ± 12 (standard deviation). Of 1418 second breast cancers diagnosed, 998 were surveillance-detected cancers and 420 were interval cancers. The recall rate was 8.8% (10 365 of 117 971; 95% CI: 8.6%, 9.0%), the cancer detection rate was 8.5 per 1000 examinations (998 of 117 971; 95% CI: 8.0, 9.0), the interval cancer rate was 3.6 per 1000 examinations (420 of 117 971; 95% CI: 3.2, 3.9), the positive predictive value of biopsy recommendation was 31.0% (998 of 3220; 95% CI: 29.4%, 32.7%), the sensitivity was 70.4% (998 of 1418; 95% CI: 67.9%, 72.7%), and the specificity was 98.1% (114 331 of 116 553; 95% CI: 98.0%, 98.2%). Compared with previously published studies, interval cancer rate was comparable with rates from 1996 to 2007 in women with a personal history of breast cancer and was higher than the published digital mammography screening benchmarks. Conclusion In transitioning from screen-film to digital mammography and digital breast tomosynthesis, surveillance mammography performance demonstrated minimal improvement over time and remained inferior to the performance of screening mammography benchmarks. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Moy and Gao in this issue.

ObjectiveTo assess leukemia risks among children with Down syndrome in a large, contemporary cohort.Study designRetrospective cohort study including 3 905 399 children born 1996-2016 in 7 US healthcare systems or Ontario, Canada, and followed from birth to cancer diagnosis, death, age 15 years, disenrollment, or December 30, 2016. Down syndrome was identified using International Classification of Diseases, Ninth and Tenth Revisions, diagnosis codes. Cancer diagnoses were identified through linkages to tumor registries. Incidence and hazard ratios (HRs) of leukemia were estimated for children with Down syndrome and other children adjusting for health system, child's age at diagnosis, birth year, and sex.ResultsLeukemia was diagnosed in 124 of 4401 children with Down syndrome and 1941 of 3 900 998 other children. In children with Down syndrome, the cumulative incidence of acute myeloid leukemia (AML) was 1405/100 000 (95% CI 1076-1806) at age 4 years and unchanged at age 14 years. The cumulative incidence of acute lymphoid leukemia in children with Down syndrome was 1059/100 000 (95% CI 755-1451) at age 4 and 1714/100 000 (95% CI 1264-2276) at age 14 years. Children with Down syndrome had a greater risk of AML before age 5 years than other children (HR 399, 95% CI 281-566). Largest HRs were for megakaryoblastic leukemia before age 5 years (HR 1500, 95% CI 555-4070). Children with Down syndrome had a greater risk of acute lymphoid leukemia than other children regardless of age (

BackgroundChildren with central nervous system (CNS) tumors undergo frequent imaging for diagnosis and follow-up, but few studies have characterized longitudinal imaging patterns. We described medical imaging in children before and after malignant CNS tumor diagnosis.ProcedureWe conducted a retrospective cohort study of children aged 0-20 years diagnosed with CNS tumors between 1996-2016 at six U.S. integrated healthcare systems and Ontario, Canada. We collected computed topography (CT), magnetic resonance imaging (MRI), radiography, ultrasound, nuclear medicine examinations from 12 months before through 10 years after CNS diagnosis censoring six months before death or a subsequent cancer diagnosis, disenrollment from the health system, age 21 years, or December 31, 2016. We calculated imaging rates per child per month stratified by modality, country, diagnosis age, calendar year, time since diagnosis, and tumor grade.ResultsWe observed 1,879 children with median four years follow-up post-diagnosis in the U.S. and seven years in Ontario, Canada. During the diagnosis period (±15 days of diagnosis), children averaged 1.10 CTs (95% confidence interval [CI] 1.09-1.13) and 2.14 MRIs (95%CI 2.12-2.16) in the U.S., and 1.67 CTs (95%CI 1.65-1.68) and 1.86 MRIs (95%CI 1.85-1.88) in Ontario. Within one year after diagnosis, 19% of children had ≥5 CTs and 45% had ≥5 MRIs. By nine years after diagnosis, children averaged one MRI and one radiograph per year with little use of other imaging modalities.ConclusionsMRI and CT are commonly used for CNS tumor diagnosis, whereas MRI is the primary modality used during surveillance of children with CNS tumors.

In response to calls to reduce unnecessary diagnostic testing with computed tomographic pulmonary angiography (CTPA) for suspected pulmonary embolism (PE), there have been growing efforts to create and implement decision rules for PE testing. It is unclear if the use of advanced imaging tests for PE has diminished over time.To assess the use of advanced imaging tests, including chest computed tomography (CT) (ie, all chest CT except for CTPA), CTPA, and ventilation-perfusion (V/Q) scan, for PE from 2004 to 2016.Cohort study of adults by age group (18-64 years and ≥65 years) enrolled in 7 US integrated and mixed-model health care systems. Joinpoint regression analysis was used to identify years with statistically significant changes in imaging rates and to calculate average annual percentage change (growth) from 2004 to 2007, 2008 to 2011, and 2012 to 2016. Analyses were conducted between June 11, 2019, and March 18, 2020.Rates of chest CT, CTPA, and V/Q scan by year and age, as well as annual change in rates over time.Overall, 3.6 to 4.8 million enrollees were included each year of the study, for a total of 52 343 517 person-years of follow-up data. Adults aged 18 to 64 years accounted for 42 223 712 person-years (80.7%) and those 65 years or older accounted for 10 119 805 person-years (19.3%). Female enrollees accounted for 27 712 571 person-years (52.9%). From 2004 and 2016, chest CT use increased by 66.3% (average annual growth, 4.4% per year), CTPA use increased by 450.0% (average annual growth, 16.3% per year), and V/Q scan use decreased by 47.1% (decreasing by 4.9% per year). The use of CTPA increased most rapidly from 2004 to 2006 (44.6% in those aged 18-64 years and 43.9% in those ≥65 years), with ongoing rapid growth from 2006 to 2010 (annual growth, 19.8% in those aged 18-64 years and 18.3% in those ≥65 years) and persistent but slower growth in the most recent years (annual growth, 4.3% in those aged 18-64 years and 3.0% in those ≥65 years from 2010 to 2016). The use of V/Q scanning decreased steadily since 2004.From 2004 to 2016, rates of chest CT and CTPA for suspected PE continued to increase among adults but at a slower pace in more contemporary years. Efforts to combat overuse have not been completely successful as reflected by ongoing growth, rather than decline, of chest CT use. Whether the observed imaging use was appropriate or was associated with improved patient outcomes is unknown.

Background: Greater than 10% of hospitalized MRSA carriers experience serious MRSA infection in the year following discharge. Prevention opportunities have primarily focused on hospital stays; however postdischarge interventions have the potential to reduce morbidity, mortality and healthcare costs. The CLEAR trial found a 30% hazard reduction in postdischarge MRSA infections among patients who had inpatient MRSA cultures and were given postdischarge decolonization (5 days twice-a-month for 6 months) relative to hygiene education alone. We conducted a cost analysis of the CLEAR intervention to quantify the economic implications and understand the value of adopting this MRSA decolonization strategy. Methods: We constructed a decision model to estimate the one-year healthcare utilization and costs associated with postdischarge decolonization relative to hygiene education. Trial results for MRSA infection risk and downstream outcomes (including outpatient and emergency room visits, hospitalizations, related nursing home stays, and postdischarge antibiotics) were used to parameterize the model. Other medical care and prescription drug costs were based on Medicare Fee Schedules, Red Book and the literature. Patient out-of-pocket costs and time costs associated with subsequent infections were from a survey of trial participants experiencing infection (n=405). All costs were reported in 2019 US dollars. The analysis was conducted using healthcare system and societal perspectives. Sensitivity analyses were conducted on key parameters. Results: Among a hypothetical cohort of 1,000 hospitalized MRSA carriers, we estimated that a postdischarge decolonization intervention versus hygiene education would result in at least 36 fewer subsequent MRSA infections (130 vs 93 of 1,000, respectively) and >40 fewer MRSA-attributable healthcare events including 32 hospitalizations and 6 postdischarge nursing home visits over the course of a year. Assuming an intervention cost of $185 per individual, the program would result in an overall cost savings of $469,000 per 1,000 MRSA carriers undergoing decolonization. This translates to an overall savings of $13,200 per infection averted and $9,000 per infection averted from the healthcare system perspective. Even assuming a lower infection rate or a less effective intervention (15% reduction in infections vs 30% in the CLEAR trial), or a more expensive (up to $653 per patient) intervention, a decolonization program would still result in cost-savings for society, the healthcare system and patients. Conclusions: In addition to health benefits of preventing infections, postdischarge decolonization of MRSA carriers yields substantial savings to society and the healthcare system. Future recommendations for reducing postdischarge MRSA-related disease among MRSA carriers should consider routine decolonization at hospital discharge. Funding: This study was supported by a grant from the AHRQ Healthcare-Associated Infections Program (R01HS019388) and by the University of California Irvine Institute for Clinical and Translational Science, which was funded by a grant from the NIH Clinical and Translational Sciences Award program (UL1 TR000153). Disclosures: Dr. Huang reports conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), Mölnlycke, 3M, Clorox, Xttrium Laboratories, and Medline. Ms. Singh reports conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories, and Medline. Dr. Rashid, conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker(Sage Products), Clorox, and Medline. Dr. McKinnell reports receiving grant support to his institution from Melinta Therapeutics, and fees for serving as a research investigator from Lightship, conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories and Medline, and serving as cofounder of Expert Stewardship. Dr. Miller reports receiving grant support from Gilead Sciences, Merck, Abbott, Cepheid, Genentech, Atox Bio, and Paratek Pharmaceuticals, grant support and fees for serving on an advisory board from Achaogen and grant support, consulting fees, and fees for serving on an advisory board from Tetraphase and conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories, and Medline.

BackgroundSurveillance with annual mammography and breast magnetic resonance imaging (MRI) is recommended for female survivors of childhood cancer treated with chest radiation, yet benefits, harms, and costs are uncertain.ObjectiveTo compare the benefits, harms, and cost-effectiveness of breast cancer screening strategies in childhood cancer survivors.DesignCollaborative simulation modeling using 2 Cancer Intervention and Surveillance Modeling Network breast cancer models.Data sourcesChildhood Cancer Survivor Study and published data.Target populationWomen aged 20 years with a history of chest radiotherapy.Time horizonLifetime.PerspectivePayer.InterventionAnnual MRI with or without mammography, starting at age 25, 30, or 35 years.Outcome measuresBreast cancer deaths averted, false-positive screening results, benign biopsy results, and incremental cost-effectiveness ratios (ICERs).Results of base-case analysisLifetime breast cancer mortality risk without screening was 10% to 11% across models. Compared with no screening, starting at age 25 years, annual mammography with MRI averted the most deaths (56% to 71%) and annual MRI (without mammography) averted 56% to 62%. Both strategies had the most screening tests, false-positive screening results, and benign biopsy results. For an ICER threshold of less than $100 000 per quality-adjusted life-year gained, screening beginning at age 30 years was preferred.Results of sensitivity analysisAssuming lower screening performance, the benefit of adding mammography to MRI increased in both models, although the conclusions about preferred starting age remained unchanged.LimitationElevated breast cancer risk was based on survivors diagnosed with childhood cancer between 1970 and 1986.ConclusionEarly initiation (at ages 25 to 30 years) of annual breast cancer screening with MRI, with or without mammography, might reduce breast cancer mortality by half or more in survivors of childhood cancer.Primary funding sourceAmerican Cancer Society and National Institutes of Health.

BackgroundDigital breast tomosynthesis (DBT) is increasingly being used for routine breast cancer screening. We projected the long-term impact and cost-effectiveness of DBT compared to conventional digital mammography (DM) for breast cancer screening in the United States.MethodsThree Cancer Intervention and Surveillance Modeling Network breast cancer models simulated US women ages 40 years and older undergoing breast cancer screening with either DBT or DM starting in 2011 and continuing for the lifetime of the cohort. Screening performance estimates were based on observational data; in an alternative scenario, we assumed 4% higher sensitivity for DBT. Analyses used federal payer perspective; costs and utilities were discounted at 3% annually. Outcomes included breast cancer deaths, quality-adjusted life-years (QALYs), false-positive examinations, costs, and incremental cost-effectiveness ratios (ICERs).ResultsCompared to DM, DBT screening resulted in a slight reduction in breast cancer deaths (range across models 0-0.21 per 1000 women), small increase in QALYs (1.97-3.27 per 1000 women), and a 24-28% reduction in false-positive exams (237-268 per 1000 women) relative to DM. ICERs ranged from $195 026 to $270 135 per QALY for DBT relative to DM. When assuming 4% higher DBT sensitivity, ICERs decreased to $130 533-$156 624 per QALY. ICERs were sensitive to DBT costs, decreasing to $78 731 to $168 883 and $52 918 to $118 048 when the additional cost of DBT was reduced to $36 and $26 (from baseline of $56), respectively.ConclusionDBT reduces false-positive exams while achieving similar or slightly improved health benefits. At current reimbursement rates, the additional costs of DBT screening are likely high relative to the benefits gained; however, DBT could be cost-effective at lower screening costs.

PurposeGreat uncertainty exists about the costs associated with whole-genome sequencing (WGS).MethodsOne hundred cardiology patients with cardiomyopathy diagnoses and 100 ostensibly healthy primary care patients were randomized to receive a family-history report alone or with a WGS report. Cardiology patients also reviewed prior genetic test results. WGS costs were estimated by tracking resource use and staff time. Downstream costs were estimated by identifying services in administrative data, medical records, and patient surveys for 6 months.ResultsThe incremental cost per patient of WGS testing was $5,098 in cardiology settings and $5,073 in primary care settings compared with family history alone. Mean 6-month downstream costs did not differ statistically between the control and WGS arms in either setting (cardiology: difference = -$1,560, 95% confidence interval -$7,558 to $3,866, p = 0.36; primary care: difference = $681, 95% confidence interval -$884 to $2,171, p = 0.70). Scenario analyses showed the cost reduction of omitting or limiting the types of secondary findings was less than $69 and $182 per patient in cardiology and primary care, respectively.ConclusionShort-term costs of WGS were driven by the costs of sequencing and interpretation rather than downstream health care. Disclosing additional types of secondary findings has a limited cost impact following disclosure.

Background: Increase in breast cancer incidence associated with mammography screening diffusion may have attenuated risk associations between family history and breast cancer.Methods: The proportions of women ages 40 to 74 years reporting a first-degree family history of breast cancer were estimated in the Breast Cancer Surveillance Consortium cohort (BCSC: N = 1,170,900; 1996-2012) and the Collaborative Breast Cancer Study (CBCS: cases N = 23,400; controls N = 26,460; 1987-2007). Breast cancer (ductal carcinoma in situ and invasive) relative risk estimates and 95% confidence intervals (CI) associated with family history were calculated using multivariable Cox proportional hazard and logistic regression models.Results: The proportion of women reporting a first-degree family history increased from 11% in the 1980s to 16% in 2010 to 2013. Family history was associated with a >60% increased risk of breast cancer in the BCSC (HR, 1.61; 95% CI, 1.55-1.66) and CBCS (OR, 1.64; 95% CI, 1.57-1.72). Relative risks decreased slightly with age. Consistent trends in relative risks were not observed over time or across stage of disease at diagnosis in both studies, except among older women (ages 60-74) where estimates were attenuated from about 1.7 to 1.3 over the last 20 years (P trend = 0.08 for both studies).Conclusions: Although the proportion of women with a first-degree family history of breast cancer increased over time and by age, breast cancer risk associations with family history were nonetheless fairly constant over time for women under age 60.Impact: First-degree family history of breast cancer remains an important breast cancer risk factor, especially for younger women, despite its increasing prevalence in the mammography screening era. Cancer Epidemiol Biomarkers Prev; 26(12); 1753-60. ©2017 AACR.

BackgroundControversy persists about optimal mammography screening strategies.ObjectiveTo evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer.DesignCollaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality.SettingUnited States.PatientsAverage-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity.InterventionEight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years.MeasurementsBenefits (breast cancer-specific mortality reduction, breast cancer deaths averted, life-years, and quality-adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens.ResultsBiennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar benefits, but more harms than other strategies). For groups with a 2- to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years.LimitationOther imaging technologies, polygenic risk, and nonadherence were not considered.ConclusionBiennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the decision makers' weight given to the harms and benefits of screening.Primary funding sourceNational Institutes of Health.

PurposeTo evaluate the effectiveness of combined biennial digital mammography and tomosynthesis screening, compared with biennial digital mammography screening alone, among women with dense breasts.Materials and methodsAn established, discrete-event breast cancer simulation model was used to estimate the comparative clinical effectiveness and cost-effectiveness of biennial screening with both digital mammography and tomosynthesis versus digital mammography alone among U.S. women aged 50-74 years with dense breasts from a federal payer perspective and a lifetime horizon. Input values were estimated for test performance, costs, and health state utilities from the National Cancer Institute Breast Cancer Surveillance Consortium, Medicare reimbursement rates, and medical literature. Sensitivity analyses were performed to determine the implications of varying key model parameters, including combined screening sensitivity and specificity, transient utility decrement of diagnostic work-up, and additional cost of tomosynthesis.ResultsFor the base-case analysis, the incremental cost per quality-adjusted life year gained by adding tomosynthesis to digital mammography screening was $53 893. An additional 0.5 deaths were averted and 405 false-positive findings avoided per 1000 women after 12 rounds of screening. Combined screening remained cost-effective (less than $100 000 per quality-adjusted life year gained) over a wide range of incremental improvements in test performance. Overall, cost-effectiveness was most sensitive to the additional cost of tomosynthesis.ConclusionBiennial combined digital mammography and tomosynthesis screening for U.S. women aged 50-74 years with dense breasts is likely to be cost-effective if priced appropriately (up to $226 for combined examinations vs $139 for digital mammography alone) and if reported interpretive performance metrics of improved specificity with tomosynthesis are met in routine practice.

BackgroundMany states have laws requiring mammography facilities to tell women with dense breasts and negative results on screening mammography to discuss supplemental screening tests with their providers. The most readily available supplemental screening method is ultrasonography, but little is known about its effectiveness.ObjectiveTo evaluate the benefits, harms, and cost-effectiveness of supplemental ultrasonography screening for women with dense breasts.DesignComparative modeling with 3 validated simulation models.Data sourcesSurveillance, Epidemiology, and End Results Program; Breast Cancer Surveillance Consortium; and medical literature.Target populationContemporary cohort of women eligible for routine screening.Time horizonLifetime.PerspectivePayer.InterventionSupplemental ultrasonography screening for women with dense breasts after a negative screening mammography result.Outcome measuresBreast cancer deaths averted, quality-adjusted life-years (QALYs) gained, biopsies recommended after a false-positive ultrasonography result, and costs.Results of base-case analysisSupplemental ultrasonography screening after a negative mammography result for women aged 50 to 74 years with heterogeneously or extremely dense breasts averted 0.36 additional breast cancer deaths (range across models, 0.14 to 0.75), gained 1.7 QALYs (range, 0.9 to 4.7), and resulted in 354 biopsy recommendations after a false-positive ultrasonography result (range, 345 to 421) per 1000 women with dense breasts compared with biennial screening by mammography alone. The cost-effectiveness ratio was $325,000 per QALY gained (range, $112,000 to $766,000). Supplemental ultrasonography screening for only women with extremely dense breasts cost $246,000 per QALY gained (range, $74,000 to $535,000).Results of sensitivity analysisThe conclusions were not sensitive to ultrasonography performance characteristics, screening frequency, or starting age.LimitationProvider costs for coordinating supplemental ultrasonography were not considered.ConclusionSupplemental ultrasonography screening for women with dense breasts would substantially increase costs while producing relatively small benefits.Primary funding sourceNational Cancer Institute.

BackgroundCompared with film, digital mammography has superior sensitivity but lower specificity for women aged 40 to 49 years and women with dense breasts. Digital has replaced film in virtually all US facilities, but overall population health and cost from use of this technology are unclear.MethodsUsing five independent models, we compared digital screening strategies starting at age 40 or 50 years applied annually, biennially, or based on density with biennial film screening from ages 50 to 74 years and with no screening. Common data elements included cancer incidence and test performance, both modified by breast density. Lifetime outcomes included mortality, quality-adjusted life-years, and screening and treatment costs.ResultsFor every 1000 women screened biennially from age 50 to 74 years, switching to digital from film yielded a median within-model improvement of 2 life-years, 0.27 additional deaths averted, 220 additional false-positive results, and $0.35 million more in costs. For an individual woman, this translates to a health gain of 0.73 days. Extending biennial digital screening to women ages 40 to 49 years was cost-effective, although results were sensitive to quality-of-life decrements related to screening and false positives. Targeting annual screening by density yielded similar outcomes to targeting by age. Annual screening approaches could increase costs to $5.26 million per 1000 women, in part because of higher numbers of screens and false positives, and were not efficient or cost-effective.ConclusionsThe transition to digital breast cancer screening in the United States increased total costs for small added health benefits. The value of digital mammography screening among women aged 40 to 49 years depends on women's preferences regarding false positives.