Longitudinal humoral analysis in RSV-infected infants identifies pre-existing RSV strain-specific G and evolving cross-reactive F antibodies.

Respiratory syncytial virus (RSV) is among the most common causes of lower respiratory tract infection (LRTI) and hospitalization in infants. However, the mechanisms of immune control in infants remain incompletely understood. Antibody profiling against attachment (G) and fusion (F) proteins in children less than 2 years of age, with mild (outpatients) or severe (inpatients) RSV disease, indicated substantial age-dependent differences in RSV-specific immunity. Maternal antibodies were detectable for the first 3 months of life, followed by a long window of immune vulnerability between 3 and 6 months and a rapid evolution of FcγR-recruiting immunity after 6 months of age. Acutely ill hospitalized children exhibited lower G-specific antibodies compared with healthy controls. With disease resolution, RSV-infected infants generated broad functional RSV strain-specific G-responses and evolved cross-reactive F-responses, with minimal maternal imprinting. These data suggest an age-independent RSV G-specific functional humoral correlate of protection, and the evolution of RSV F-specific functional immunity with disease resolution.

Cancer diagnosis and treatment in working-age adults: Implications for employment, health insurance coverage, and financial hardship in the United States.

The rising costs of cancer care and subsequent medical financial hardship for cancer survivors and families are well documented in the United States. Less attention has been paid to employment disruptions and loss of household income after a cancer diagnosis and during treatment, potentially resulting in lasting financial hardship, particularly for working-age adults not yet age-eligible for Medicare coverage and their families. In this article, the authors use a composite patient case to illustrate the adverse consequences of cancer diagnosis and treatment for employment, health insurance coverage, household income, and other aspects of financial hardship. They summarize existing research and provide nationally representative estimates of multiple aspects of financial hardship and health insurance coverage, benefit design, and employee benefits, such as paid sick leave, among working-age adults with a history of cancer and compare them with estimates among working-age adults without a history of cancer from the most recently available years of the National Health Interview Survey (2019-2021). Then, the authors identify opportunities for addressing employment and health insurance coverage challenges at multiple levels, including federal, state, and local policies; employers; cancer care delivery organizations; and nonprofit organizations. These efforts, when informed by research to identify best practices, can potentially help mitigate the financial hardship associated with cancer.

Time to add screening for financial hardship as a quality measure?

Cancer treatment is associated with financial hardship for many patients and families. Screening for financial hardship and referrals to appropriate resources for mitigation are not currently part of most clinical practices. In fact, discussions regarding the cost of treatment occur infrequently in clinical practice. As the cost of cancer treatment continues to rise, the need to mitigate adverse consequences of financial hardship grows more urgent. The introduction of quality measurement and reporting has been successful in establishing standards of care, reducing disparities in receipt of care, and improving other aspects of cancer care outcomes within and across providers. The authors propose the development and adoption of financial hardship screening and management as an additional quality metric for oncology practices. They suggest relevant stakeholders, conveners, and approaches for developing, testing, and implementing a screening and management tool and advocate for endorsement by organizations such as the National Quality Forum and professional societies for oncology care clinicians. The confluence of increasingly high-cost care and widening disparities in ability to pay because of underinsurance and lack of health insurance coverage makes a strong argument to take steps to mitigate the financial consequences of cancer.

Cervical cancer screening for individuals at average risk: 2020 guideline update from the American Cancer Society.

The American Cancer Society (ACS) recommends that individuals with a cervix initiate cervical cancer screening at age 25 years and undergo primary human papillomavirus (HPV) testing every 5 years through age 65 years (preferred); if primary HPV testing is not available, then individuals aged 25 to 65 years should be screened with cotesting (HPV testing in combination with cytology) every 5 years or cytology alone every 3 years (acceptable) (strong recommendation). The ACS recommends that individuals aged >65 years who have no history of cervical intraepithelial neoplasia grade 2 or more severe disease within the past 25 years, and who have documented adequate negative prior screening in the prior 10 years, discontinue all cervical cancer screening (qualified recommendation). These new screening recommendations differ in 4 important respects compared with the 2012 recommendations: 1) The preferred screening strategy is primary HPV testing every 5 years, with cotesting and cytology alone acceptable where access to US Food and Drug Administration-approved primary HPV testing is not yet available; 2) the recommended age to start screening is 25 years rather than 21 years; 3) primary HPV testing, as well as cotesting or cytology alone when primary testing is not available, is recommended starting at age 25 years rather than age 30 years; and 4) the guideline is transitional, ie, options for screening with cotesting or cytology alone are provided but should be phased out once full access to primary HPV testing for cervical cancer screening is available without barriers. Evidence related to other relevant issues was reviewed, and no changes were made to recommendations for screening intervals, age or criteria for screening cessation, screening based on vaccination status, or screening after hysterectomy. Follow-up for individuals who screen positive for HPV and/or cytology should be in accordance with the 2019 American Society for Colposcopy and Cervical Pathology risk-based management consensus guidelines for abnormal cervical cancer screening tests and cancer precursors.

Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250-281. © 2018 American Cancer Society.

CTCF is essential for proper mitotic spindle structure and anaphase segregation.

Mitosis is an essential process in which the duplicated genome is segregated equally into two daughter cells. CTCF has been reported to be present in mitosis and has a role in localizing CENP-E, but its importance for mitotic fidelity remains to be determined. To evaluate the importance of CTCF in mitosis, we tracked mitotic behaviors in wild-type and two different CTCF CRISPR-based genetic knockdowns. We find that knockdown of CTCF results in prolonged mitoses and failed anaphase segregation via time-lapse imaging of SiR-DNA. CTCF knockdown did not alter cell cycling or the mitotic checkpoint, which was activated upon nocodazole treatment. Immunofluorescence imaging of the mitotic spindle in CTCF knockdowns revealed disorganization via tri/tetrapolar spindles and chromosomes behind the spindle pole. Imaging of interphase nuclei showed that nuclear size increased drastically, consistent with failure to divide the duplicated genome in anaphase. Long-term inhibition of CNEP-E via GSK923295 recapitulates CTCF knockdown abnormal mitotic spindles with polar chromosomes and increased nuclear sizes. Population measurements of nuclear shape in CTCF knockdowns do not display decreased circularity or increased nuclear blebbing relative to wild-type. However, failed mitoses do display abnormal nuclear morphologies relative to successful mitoses, suggesting that population images do not capture individual behaviors. Thus, CTCF is important for both proper metaphase organization and anaphase segregation which impacts the size and shape of the interphase nucleus likely through its known role in recruiting CENP-E.

Longitudinal varying coefficient single-index model with censored covariates.

It is of interest to health policy research to estimate the population-averaged longitudinal medical cost trajectory from initial cancer diagnosis to death, and understand how the trajectory curve is affected by patient characteristics. This research question leads to a number of statistical challenges because the longitudinal cost data are often non-normally distributed with skewness, zero-inflation, and heteroscedasticity. The trajectory is nonlinear, and its length and shape depend on survival, which are subject to censoring. Modeling the association between multiple patient characteristics and nonlinear cost trajectory curves of varying lengths should take into consideration parsimony, flexibility, and interpretation. We propose a novel longitudinal varying coefficient single-index model. Multiple patient characteristics are summarized in a single-index, representing a patient's overall propensity for healthcare use. The effects of this index on various segments of the cost trajectory depend on both time and survival, which is flexibly modeled by a bivariate varying coefficient function. The model is estimated by generalized estimating equations with an extended marginal mean structure to accommodate censored survival time as a covariate. We established the pointwise confidence interval of the varying coefficient and a test for the covariate effect. The numerical performance was extensively studied in simulations. We applied the proposed methodology to medical cost data of prostate cancer patients from the Surveillance, Epidemiology, and End Results-Medicare-Linked Database.

Work Productivity Among Younger Breast Cancer Survivors: The Impact of Behavioral Interventions for Depression.

OBJECTIVES: The Pathways to Wellness randomized controlled trial found that 2 behavioral interventions, mindfulness awareness practices and survivorship education, reduced depressive symptoms in younger breast cancer survivors (BCSs) compared with wait-list control. This secondary analysis examines whether the interventions led to reduced loss of work productivity among younger BCSs and whether such reductions were mediated by reductions in depressive symptoms. METHODS: The Work Productivity and Activity Impairment scale was used to measure work productivity loss at 4 assessment time points. Correlates of productivity loss at enrollment were examined using multivariable linear regression. Differences in change over time in productivity loss between each intervention group and control were assessed using linear mixed models. Reduced depressive symptoms were tested as a mediator of reduced productivity loss. RESULTS: Of 247 trial participants, 199 were employed and included in the analyses. At enrollment, higher productivity loss was associated with chemotherapy receipt (P = .003), younger age (P = .021), more severe cognitive problems (P = .002), higher musculoskeletal pain severity (P = .002), more depressive symptoms (P = .016), and higher fatigue severity (P = .033). The mindfulness intervention led to significantly less productivity loss compared with control at all 3 postintervention assessment points (all P < .05), with about 54% of the effect mediated by reduction in depressive symptoms. Survivorship education was not associated with reduced loss of productivity. CONCLUSIONS: These findings suggest that addressing depressive symptoms through behavioral interventions, such as mindfulness, may mitigate impacts on work productivity in younger BCSs.

In-Clinic vs. Online Recruitment of Women with a History of Cervical Intraepithelial Neoplasia or Cervical Cancer to a Smoking Cessation Trial: A Post-hoc Comparison of Participant Characteristics, Study Retention, and Cessation Outcomes.

INTRODUCTION: Recruiting special populations to smoking cessation trials is challenging and approaches beyond in-clinic recruitment may be beneficial. This secondary analysis of data from a smoking cessation RCT for individuals with a history of cervical cancer or cervical intraepithelial neoplasia (CIN) explored differences associated with in-clinic vs. online recruitment. METHODS: Participants were recruited from clinics within a university-based NCI-designated cancer center (n=87) and online nationally via Facebook (n=115). Baseline measures included sociodemographics, smoking history, and cancer or CIN history. Study retention and smoking abstinence were assessed 12 months post-baseline. Group differences in baseline characteristics were evaluated. Retention and abstinence were evaluated while controlling for group differences and predictors. RESULTS: Participants recruited online (vs. in-clinic) had higher educational attainment (p=.01) and health literacy (p=.003). They were more likely to have CIN vs. cancer, to be further from the time of diagnosis, and to have completed active treatment (p values<.001). While controlling for these group differences and independent predictors, retention was higher among participants recruited online (log-likelihood χ2(1)=11.41, p<.001). There were no recruitment differences in self-reported (p=.90) or biochemically confirmed smoking abstinence (p=.18). CONCLUSIONS: Compared to individuals recruited in-person, individuals recruited online were more educated, had higher health literacy, and presented with a different clinical profile (i.e., more likely to have CIN vs. cancer and to have completed active treatment). There were few differences in participant characteristics between recruitment approaches, and no differences on any smoking-related variables. Online recruitment has the potential to improve enrollment of cancer survivors to smoking cessation trials. IMPLICATIONS: People with a history of CIN or cervical cancer recruited to a smoking cessation RCT online (vs. in-clinic) were more likely to have a diagnosis of CIN vs. cancer and were more educated and health literate. Participants recruited online were more likely to be retained in the study and there were no differences in smoking abstinence rates at 12-months. Incorporating online recruitment increased the reach of tobacco treatment efforts to a larger and more diverse sample. This could reduce the burden of tobacco-related disease, improve CIN and cancer treatment outcomes, and reduce secondary malignancies and morbidity among this underserved group.

Metastatic Pulmonary Calcification: Single-Center Review of Typical and Atypical Imaging Features.

PURPOSE: The purpose of this study is to bring attention to an atypical form of metastatic pulmonary calcification, which is conventionally described as a metabolic process with upper lobe predominance in patients with a specific clinical history, which has not been reported as a distinct entity. METHODS: Patients with metastatic pulmonary calcification (MPC) were first identified with mPower keyword search, including MPC or metastatic calcifications on computed tomography chest radiological reports. Patients were then filtered on likelihood of MPC based off imaging reports. Images were then reviewed by three senior radiologists for pertinent characteristics such as location of MPC, degree of calcifications and pleural effusions. Based on the predominant location of MPC, cases were labeled as either typical or atypical. Clinical and imaging characteristics relevant to MPC were noted and compared across typical and atypical cases. RESULTS: In our study, we describe 25 patients with MPC, 13 defined as typical MPC and 12 with atypical MPC. Through consensus of senior radiologists, MPC was deemed to be mild (52%), moderate (44%), or severe (4%). Twenty-three patients (92%) had underlying renal disease including 21 requiring dialysis at the time of diagnosis. Outside of age at diagnosis, there was no significant clinical difference between the two groups. Evaluation of imaging characteristics (average HU attenuation, 267; range, 186-295), pattern and distribution of calcification, and clinical history strongly supported a diagnosis of atypical MPC. CONCLUSION: This study presents several cases of lower lobe subpleural MPC associated with pleural effusions, which has not been reported as a distinct entity, despite comprising a significant portion of MPC cases at our institution.

Oncologist Participation and Performance in the Merit-Based Incentive Payment System.

The merit-based incentive payment system (MIPS) is a value-based payment model created by the Centers for Medicare & Medicaid Services (CMS) to promote high-value care through performance-based adjustments of Medicare reimbursements. In this cross-sectional study, we examined the participation and performance of oncologists in the 2019 MIPS. Oncologist participation was low (86%) compared to all-specialty participation (97%). After adjusting for practice characteristics, higher MIPS scores were observed among oncologists with alternative payment models (APMs) as their filing source (mean score, 91 for APMs vs. 77.6 for individuals; difference, 13.41 [95% CI, 12.21, 14.6]), indicating the importance of greater organizational resources for participants. Lower scores were associated with greater patient complexity (mean score, 83.4 for highest quintile vs. 84.9 for lowest quintile, difference, -1.43 [95% CI, -2.48, -0.37]), suggesting the need for better risk-adjustment by CMS. Our findings may guide future efforts to improve oncologist engagement in MIPS.

Cost-Effectiveness of Medication Therapy Management Program Across Racial and Ethnic Groups Among Medicare Beneficiaries.

OBJECTIVES: Equity and effectiveness of the medication therapy management (MTM) program in Medicare has been a policy focus since its inception. The objective of this study was to evaluate the cost-effectiveness of the Medicare MTM program in improving medication utilization quality across racial and ethnic groups. METHODS: This study analyzed 2017 Medicare data linked to the Area Health Recourses File. A propensity score was used to match MTM enrollees and nonenrollees, and an incremental cost-effectiveness ratio between the 2 groups was calculated. Effectiveness was measured as the proportion of appropriate medication utilization based on medication utilization measures developed by Pharmacy Quality Alliance. Net monetary benefits were compared across racial and ethnic groups at various societal willingness-to-pay (WTP) thresholds. The 95% confidence intervals were obtained by nonparametric bootstrapping. RESULTS: MTM dominated non-MTM among the total sample (N = 699 992), as MTM enrollees had lower healthcare costs ($31 135.89 vs $32 696.69) and higher proportions of appropriate medication utilization (87.47% vs 85.31%) than nonenrollees. MTM enrollees had both lower medication costs ($10 681.21 vs $11 003.08) and medical costs ($20 454.68 vs $21 693.61) compared with nonenrollees. The cost-effectiveness of MTM was higher among Black patients than White patients across the WTP thresholds. For instance, at a WTP of $3006 per percentage point increase in effectiveness, the net monetary benefit for Black patients was greater than White patients by $2334.57 (95% confidence interval $1606.53-$3028.85). CONCLUSIONS: MTM is cost-effective in improving medication utilization quality among Medicare beneficiaries and can potentially reduce disparities between Black and White patients. Expansion of the current MTM program could maximize these benefits.

Promises and Challenges of Next-Generation "Beyond Li-ion" Batteries for Electric Vehicles and Grid Decarbonization.

The tremendous improvement in performance and cost of lithium-ion batteries (LIBs) have made them the technology of choice for electrical energy storage. While established battery chemistries and cell architectures for Li-ion batteries achieve good power and energy density, LIBs are unlikely to meet all the performance, cost, and scaling targets required for energy storage, in particular, in large-scale applications such as electrified transportation and grids. The demand to further reduce cost and/or increase energy density, as well as the growing concern related to natural resource needs for Li-ion have accelerated the investigation of so-called "beyond Li-ion" technologies. In this review, we will discuss the recent achievements, challenges, and opportunities of four important "beyond Li-ion" technologies: Na-ion batteries, K-ion batteries, all-solid-state batteries, and multivalent batteries. The fundamental science behind the challenges, and potential solutions toward the goals of a low-cost and/or high-energy-density future, are discussed in detail for each technology. While it is unlikely that any given new technology will fully replace Li-ion in the near future, "beyond Li-ion" technologies should be thought of as opportunities for energy storage to grow into mid/large-scale applications.

Smoking cessation services and shared decision-making practices among lung cancer screening facilities: A cross-sectional study.

BACKGROUND: Little is known about how screening facilities are meeting the requirements for the reimbursement of lung cancer screening from the Centers for Medicare & Medicaid Services (CMS), including 1) the collection and submission of data to the CMS-approved registry (American College of Radiology [ACR] Lung Cancer Screening Registry), 2) the verification of a counseling and shared decision-making (SDM) visit having occurred as part of the written order for lung cancer screening with low-dose computed tomography, and 3) the offering of smoking cessation interventions. METHODS: The authors identified facilities in a southwestern state that were listed by either the ACR Lung Cancer Screening Registry or the GO2 Foundation Centers of Excellence. To select facilities, they used 2 purposive sampling approaches: maximum variation sampling and snowball sampling. They surveyed facilities from February to November 2019. RESULTS: There were 87 facilities contacted, and a total of 63 facilities representing 32 counties across Texas completed the survey. Nearly all facilities used Lung-RADS to classify nodules (92%; n = 58) and submitted data to a CMS-approved registry (92%; n = 57). Most facilities verified that the counseling and SDM visit had occurred (86%; n = 54). Although slightly more than half of the facilities reported always providing self-help cessation materials (68%; n = 42), similar or higher proportions of facilities reported that they never referred smokers to onsite cessation services (68%; n = 42) or quitlines (77%; n = 47), provided cessation counseling (81%; n = 50), or recommended medications (85%; n = 52). CONCLUSIONS: In general, screening facilities are meeting CMS requirements for screening, but they are struggling to offer smoking cessation interventions other than providing self-help materials.

Perinatal outcomes of women with gestational breast cancer in Australia and New Zealand: A prospective population-based study.

OBJECTIVE: To determine the epidemiology, clinical management, and outcomes of women with gestational breast cancer (GBC). METHODS: A population-based prospective cohort study was conducted in Australia and New Zealand between 2013 and 2014 using the Australasian Maternity Outcomes Surveillance System (AMOSS). Women who gave birth with a primary diagnosis of breast cancer during pregnancy were included. Data were collected on demographic and pregnancy factors, GBC diagnosis, obstetric and cancer management, and perinatal outcomes. The main outcome measures were preterm birth, maternal complications, breastfeeding, and death. RESULTS: Forty women with GBC (incidence 7.5/100 000 women giving birth) gave birth to 40 live-born babies. Thirty-three (82.5%) women had breast symptoms at diagnosis. Of 27 women diagnosed before 30 weeks' gestation, 85% had breast surgery and 67% had systemic therapy during pregnancy. In contrast, all 13 women diagnosed from 30 weeks had their cancer management delayed until postdelivery. There were 17 preterm deliveries; 15 were planned. Postpartum complications included the following: hemorrhage (n = 4), laparotomy (n = 1), and thrombocytopenia (n = 1). There was one late maternal death. Eighteen (45.0%) women initiated breastfeeding, including 12 of 23 women who had antenatal breast surgery. There were no perinatal deaths or congenital malformations, but 42.5% of babies were preterm, and 32.5% were admitted for higher-level neonatal care. CONCLUSIONS: Gestational breast cancer diagnosed before 30 weeks' gestation was associated with surgical and systemic cancer care during pregnancy and planned preterm birth. In contrast, cancer treatment was deferred to postdelivery for women diagnosed from 30 weeks, reflecting the complexity of managing expectant mothers with GBC in multidisciplinary care settings.

Comparison of an automated smartphone-based smoking cessation intervention versus standard quitline-delivered treatment among underserved smokers: protocol for a randomized controlled trial.

BACKGROUND: Smoking is the leading cause of preventable morbidity and mortality in the United States. Individuals with low socioeconomic status have disproportionately high smoking rates and greater difficulty quitting smoking. Efficiently connecting underserved smokers to effective tobacco cessation programs is crucial for disease prevention and the elimination of health disparities. Smartphone-based interventions have the potential to enhance the reach and efficacy of smoking cessation treatments targeting underserved smokers, but there is little efficacy data for these interventions. In this study, we will partner with a large, local hunger-relief organization to evaluate the efficacy and economic impact of a theoretically-based, fully-automated, and interactive smartphone-based smoking cessation intervention. METHODS: This study will consist of a 2-group randomized controlled trial. Participants (N = 500) will be recruited from a network of food distribution centers in West Central Florida and randomized to receive either Standard Treatment (ST, n = 250) or Automated Treatment (AT, n = 250). ST participants will be connected to the Florida Quitline for telephone-based treatment and will receive a 10-week supply of nicotine replacement therapy (NRT; transdermal patches and lozenges). AT participants will receive 10 weeks of NRT and a fully-automated smartphone-based intervention consisting of interactive messaging, images, and audiovisual clips. The AT intervention period will span 26 weeks, with 12 weeks of proactive content and 26 weeks of on-demand access. ST and AT participants will complete weekly 4-item assessments for 26 weeks and 3-, 6-, and 12-month follow-up assessments. Our primary aim is to evaluate the efficacy of AT in facilitating smoking abstinence. As secondary aims, we will explore potential mediators and conduct economic evaluations to assess the cost and/or cost-effectiveness of ST vs. AT. DISCUSSION: The overall goal of this project is to determine if AT is better at facilitating long-term smoking abstinence than ST, the more resource-intensive approach. If efficacy is established, the AT approach will be relatively easy to disseminate and for community-based organizations to scale and implement, thus helping to reduce tobacco-related health disparities. TRIAL REGISTRATION: Clinical Trials Registry NCT05004662 . Registered August 13, 2021.

Incorporating Baseline Breast Density When Screening Women at Average Risk for Breast Cancer : A Cost-Effectiveness Analysis.

BACKGROUND: Breast density classification is largely determined by mammography, making the timing of the first screening mammogram clinically important. OBJECTIVE: To evaluate the cost-effectiveness of breast cancer screening strategies that are stratified by breast density. DESIGN: Microsimulation model to generate the natural history of breast cancer for women with and those without dense breasts and assessment of the cost-effectiveness of strategies tailored to breast density and nontailored strategies. DATA SOURCES: Model parameters from the literature; statistical modeling; and analysis of Surveillance, Epidemiology, and End Results-Medicare data. TARGET POPULATION: Women aged 40 years or older. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: No screening; biennial or triennial mammography from age 50 to 75 years; annual mammography from age 50 to 75 years for women with dense breasts at age 50 years and biennial or triennial mammography from age 50 to 75 years for those without dense breasts at age 50 years; and annual mammography at age 40 to 75 years for women with dense breasts at age 40 years and biennial or triennial mammography at age 50 to 75 years for those without dense breasts at age 40 years. OUTCOME MEASURES: Lifetime costs and quality-adjusted life-years (QALYs), discounted at 3% annually. RESULTS OF BASE-CASE ANALYSIS: Baseline screening at age 40 years followed by annual screening at age 40 to 75 years for women with dense breasts and biennial screening at age 50 to 75 years for women without dense breasts was effective and cost-effective, yielding an incremental cost-effectiveness ratio of $36 200 per QALY versus the biennial strategy at age 50 to 75 years. RESULTS OF SENSITIVITY ANALYSIS: At a societal willingness-to-pay threshold of $100 000 per QALY, the probability that the density-stratified strategy at age 40 years was optimal was 56% compared with 6 other strategies. LIMITATION: Findings may not be generalizable outside the United States. CONCLUSION: The study findings advocate for breast density-stratified screening with baseline mammography at age 40 years. PRIMARY FUNDING SOURCE: National Cancer Institute.

A framework for cancer health economics research.

LAY SUMMARY: Cancer has substantial economic impacts for patients, their families and/or caregivers, employers, and the health care system. However, there is only limited understanding of how economic issues can affect access to cancer care services and the receipt of high-quality cancer care. Health economics research in cancer is particularly timely due to the large and increasing number of patients with cancer and cancer survivors, but there are many factors that may create barriers to performing cancer health economics research. This commentary has identified important topics and questions in cancer health economics research and will assist in the development of this critical field.

Patient-Reported Out-of-Pocket Costs and Financial Toxicity During Early-Phase Oncology Clinical Trials.

BACKGROUND: Clinical trials are an important therapeutic option for patients with cancer. Although financial burden in cancer treatment is well documented, the financial burden associated with clinical trials is not well understood. PATIENTS AND METHODS: We conducted a survey regarding economic burden and financial toxicity in patients with cancer enrolled in phase I clinical trials for >1 month. Financial toxicity score was assessed using the Comprehensive Score for Financial Toxicity survey. Patients also reported monthly out-of-pocket (OOP) costs. RESULTS: Two hundred and thirteen patients completed the survey (72% non-Hispanic White; 45% with annual income ≤$60,000; 50% lived >300 miles from the clinic; 37% required air travel). Forty-eight percent of patients had monthly OOP costs of at least $1,000. Fifty-five percent and 64% of patients reported unanticipated medical and nonmedical expenses, respectively. Worse financial toxicity was associated with yearly household income <$60,000 (odds ratio [OR]: 2.7; p = .008), having unanticipated medical costs (OR: 3.2; p = .024), and living >100 miles away from the clinical trial hospital (OR: 2.3; p = .043). Non-White or Hispanic patients (OR: 2.5; p = .011) and patients who were unemployed or not working outside the home (OR: 2.5; p = .016) were more likely to report high unanticipated medical costs. CONCLUSION: Among patients with cancer participating in clinical trials, economic burden is high, and most of patients' OOP costs were nonmedical costs. Financial toxicity is disproportionally higher in patients with lower income and those who travel farther, and unexpected medical costs were more common among non-White or Hispanic patients. OOP costs can be substantial and are often unexpected for patients. IMPLICATIONS FOR PRACTICE: The financial burden of cancer treatment is well documented, but there are limited data regarding the financial burden associated with cancer clinical trials. This study surveyed 213 patients enrolled in early-phase clinical trials. Monthly out-of-pocket costs were at least $1000 for nearly half of patients. Worse financial toxicity was associated with income <$60,000 and living farther away from the hospital. Racial/ethnic minorities had higher rates of unanticipated medical costs. These data help to quantify the high financial burden for patients and may reveal a cause of disparities in clinical trial enrollment for underrepresented populations.

High-throughput single-cell DNA sequencing of acute myeloid leukemia tumors with droplet microfluidics.

To enable the characterization of genetic heterogeneity in tumor cell populations, we developed a novel microfluidic approach that barcodes amplified genomic DNA from thousands of individual cancer cells confined to droplets. The barcodes are then used to reassemble the genetic profiles of cells from next-generation sequencing data. By using this approach, we sequenced longitudinally collected acute myeloid leukemia (AML) tumor populations from two patients and genotyped up to 62 disease relevant loci across more than 16,000 individual cells. Targeted single-cell sequencing was able to sensitively identify cells harboring pathogenic mutations during complete remission and uncovered complex clonal evolution within AML tumors that was not observable with bulk sequencing. We anticipate that this approach will make feasible the routine analysis of AML heterogeneity, leading to improved stratification and therapy selection for the disease.