RAS Amplification as a Negative Predictor of Benefit from Anti-EGFR-Containing Therapy Regimens in Metastatic Colorectal Cancer.

BACKGROUND: RAS short variant (SV) mutations in colorectal cancer (CRC) are associated with lack of benefit from epidermal growth factor receptor (EGFR) monoclonal antibody (EGFRmAb). However, the clinical implications for RAS amplification (RASa) as a biomarker for anti-EGFR therapy in CRC remain ill defined. METHODS: Genomic analysis was performed using the Foundation Medicine (FM) comprehensive genomic profiling database of 37,233 CRC cases. Clinical outcomes were assessed using two independent cohorts: the City of Hope (COH) cohort of 338 patients with metastatic CRC (mCRC) and the Flatiron Health-FM real-world clinicogenomic database (CGDB) of 3,904 patients with mCRC. RESULTS: RASa was detected in 1.6% (614/37,233) of primarily mCRC. RASa 6-9 (n = 241, 39%), 10-19 (n = 165, 27%), and ≥ 20 (n = 209, 34%) copy number subsets had co-RAS SV/BRAF V600E in 63%/3%, 31%/0.6%, and 4.8%/0% of cases, respectively. In the COH cohort, six patients with RASa (13-54 copies) received EGFRmAb, four of six had progressive disease, two had stable disease, and median time to treatment discontinuation (TTD) was 2.5 months. Of the CGDB EGFRmAb-treated patients, those with RASa (n = 9) had median TTD of 4.7 months and overall survival (OS) of 11.4 months, those with RAS SV (n = 101) had median TTD and OS of 5.3 and 9.4 months, and those with RAS/BRAF wild-type (n = 608) had median TTD and OS of 7.6 and 13.7 months. CONCLUSION: Patients with RASa without RAS mutations (1.1% of mCRC) may have poor outcomes on EGFRmAb, although numbers herein were small, and interpretation is confounded by combination chemotherapy. Larger independent studies are warranted to determine if RASa, including degree of amplification, may act similarly to RAS mutation as a resistance mechanism to EGFRmAb therapies. IMPLICATIONS FOR PRACTICE: Genomic data suggest that RAS amplification occurs as the sole RAS/RAF alteration in >1% of colorectal cancer cases and that degree of amplification inversely correlates with co-occurring MAPK pathway alterations. Preliminary clinical evidence suggests that RAS amplification may function similarly to RAS mutation as a negative predictor of benefit from anti-epidermal growth factor receptor therapies in colorectal cancer. More clinical data are needed, and comprehensive genomic profiling, including detection of RAS amplification, should be used in trial design to inform therapy selection.

Bayesian additional evidence for decision making under small sample uncertainty.

BACKGROUND: Statistical inference based on small datasets, commonly found in precision oncology, is subject to low power and high uncertainty. In these settings, drawing strong conclusions about future research utility is difficult when using standard inferential measures. It is therefore important to better quantify the uncertainty associated with both significant and non-significant results based on small sample sizes. METHODS: We developed a new method, Bayesian Additional Evidence (BAE), that determines (1) how much additional supportive evidence is needed for a non-significant result to reach Bayesian posterior credibility, or (2) how much additional opposing evidence is needed to render a significant result non-credible. Although based in Bayesian analysis, a prior distribution is not needed; instead, the tipping point output is compared to reasonable effect ranges to draw conclusions. We demonstrate our approach in a comparative effectiveness analysis comparing two treatments in a real world biomarker-defined cohort, and provide guidelines for how to apply BAE in practice. RESULTS: Our initial comparative effectiveness analysis results in a hazard ratio of 0.31 with 95% confidence interval (0.09, 1.1). Applying BAE to this result yields a tipping point of 0.54; thus, an observed hazard ratio of 0.54 or smaller in a replication study would result in posterior credibility for the treatment association. Given that effect sizes in this range are not extreme, and that supportive evidence exists from a similar published study, we conclude that this problem is worthy of further research. CONCLUSIONS: Our proposed method provides a useful framework for interpreting analytic results from small datasets. This can assist researchers in deciding how to interpret and continue their investigations based on an initial analysis that has high uncertainty. Although we illustrated its use in estimating parameters based on time-to-event outcomes, BAE easily applies to any normally-distributed estimator, such as those used for analyzing binary or continuous outcomes.

Real-world association of HER2/ERBB2 concordance with trastuzumab clinical benefit in advanced esophagogastric cancer.

Aim: To assess concordance between HER2 status measured by traditional methods and ERBB2 amplification measured by next-generation sequencing and its association with first-line trastuzumab clinical benefit in patients with advanced esophagogastric cancer. Methods: Retrospective analysis of HER2/ERBB2 concordance using a deidentified USA-based clinicogenomic database. Clinical outcomes were assessed for patients with HER2+ advanced esophagogastric cancer who received first-line trastuzumab. Results: Overall HER2/ERBB2 concordance was 87.5%. Among patients who received first-line trastuzumab, concordant HER2/ERBB2 was associated with longer time to treatment discontinuation (adjusted hazard ratio [aHR]: 0.63; 95% CI: 0.43-0.90) and overall survival (aHR: 0.51; 95% CI: 0.33-0.79). ERBB2 copy number ≥25 (median) was associated with longer time to treatment discontinuation (aHR: 0.56; 95% CI: 0.35-0.88) and overall survival (aHR: 0.52; 95% CI: 0.30-0.91). Conclusion: HER2/ERBB2 concordance and higher ERBB2 copy number predicted clinical benefit from trastuzumab.

Lay abstract Trastuzumab is a drug that has been shown to prolong survival in some patients with advanced esophagogastric cancer whose tumor expresses a protein biomarker called HER2. There are different methods for assessing whether a patient's tumor expresses HER2, including but not limited to traditional methods such as immunohistochemistry and in situ hybridization and novel methods such as next-generation sequencing, which detects alterations in the gene (ERBB2) that encodes the HER2 protein. In our study, we assessed concordance between HER2 status (HER2-positive or HER2-negative) measured by traditional methods and ERBB2 amplification measured by next-generation sequencing, to determine whether there was an association between concordance and clinical benefit in patients with advanced esophagogastric cancer treated with trastuzumab. Our results suggest that, when HER2 positivity is detected through traditional methods, both ERBB2 concordance (i.e., agreement that a patient's tumor had the biomarker) and a higher ERBB2 copy number (the amount of the ERBB2 gene expressed by the tumor) were associated with longer time to treatment discontinuation and overall survival in patients with advanced esophagogastric cancer treated with first-line trastuzumab.

Outcomes of the Adelante community social marketing campaign for Latino youth.

The authors designed and evaluated an innovative, branded campaign called 'Adelante' to promote positive youth development (PYD) and reduce risk behaviors among Latino youth near Washington, DC. Repeated cross-sectional surveys were conducted in the intervention and a comparison community to evaluate campaign exposure and changes in PYD outcomes. The sample consisted of 1549 Latino and immigrant adolescents surveyed at three time points in intervention and comparison communities. A social marketing campaign was implemented using outdoor advertising, Web, video and social media channels to promote PYD and health outcomes over a 1-year period from 2015 to 2016. Measures included media use; self-reported exposure to campaign promotions; Adelante message receptivity; validated PYD scales; substance use, sexual risk taking, violence-related knowledge, attitudes, beliefs, intentions and risk behavior. Outcomes were regressed first on campaign exposure to examine dose-response effects of the Adelante campaign over time. Second, we compared outcomes between the Adelante and comparison communities. We observed a positive effect of self-reported exposure on multiple outcomes, including improvements in pro-violence and sexual risk outcomes and lower pro-violence attitudes and lower risky attitudes toward sex. Adelante was effective in improving youth risk outcomes and offers a promising model for future health promotion with Latino and immigrant populations.

The Mediating Effect of Adelante brand equity on Latino Immigrant Positive Youth Development Outcomes.

This paper reports on mediation analysis of effects of the Adelante brand, an innovative program for Latino immigrant adolescents and their families, and positive youth development (PYD) outcomes. Specific objectives were to increase adolescent engagement and participation in a community-based program called Adelante, based on PYD theory, which sought to reduce substance use, sexual risk taking, and interpersonal violence among Latino immigrant youth. A total of 238 parent-child dyads were recruited from a predominantly low-income Latino immigrant community and followed for an average of 22 months. Measures included demographics; acculturation; stress and coping; social support; violence, substance use, and sexual risk attitudes; future expectations; the Adelante brand equity scale; and PYD asset measures. Multiple regression modeling shows that the leadership brand equity construct is associated with decreased proviolence and increased antiviolence attitudes. Additionally, having any program exposure (vs. none) is associated with improved substance abuse attitudes in models adjusting for the loyalty brand equity construct. In mediation analysis, we observed a mediating effect of the leadership brand equity construct on improved antiviolence attitudes among those exposed to the Adelante program. As found in previous research, Adelante brand equity operated as a mediator of program effects on Latino youth PYD outcomes.

Design and Feasibility Testing of the truth FinishIt Tobacco Countermarketing Brand Equity Scale.

The original truth campaign was a branded, national smoking prevention mass media effort focused on at-risk youth ages 12-17. Today the truth brand focuses on the goal of finishing tobacco (truth FinishIt). There have been significant changes in the tobacco control landscape, leading FinishIt to focus on 15- to 21-year-olds. The present article reports on formative research and media monitoring data collected to pilot test a new truth FinishIt brand equity scale. The goals of this study were to (a) content analyze truth FinishIt mass media ads, (b) assess truth's social media and followers' perceptions of truth's digital brand identity, and (c) develop and feasibility test a new version of the truth FinishIt brand equity scale using data from an existing Truth Initiative media monitoring study. Through factor analysis, we identified a brand equity scale, as in previous research, consisting of 4 main constructs: brand loyalty, leadership/satisfaction, personality, and awareness. Targeted truth attitudes and beliefs about social perceptions, acceptability, and industry-related beliefs were regressed on the higher order factor and each of the 4 individual brand equity factors. Ordinary least squares regression models generally showed associations in the expected directions (positive for anti-tobacco and negative for pro-tobacco) between targeted attitudes/beliefs and truth FinishIt brand equity. This study succeeded in developing and validating a new truth FinishIt brand equity scale. The scale may be a valuable metric for future campaign evaluation. Future studies should examine the effects of truth FinishIt brand equity on tobacco use behavioral outcomes over time.

The 5-4-3-2-1 go! Brand to promote nutrition and physical activity: a case of positive behavior change but negative change in beliefs.

In recent years, community-based obesity prevention programs have taken an ecological approach and addressed social determinants of obesity. The branded 5-4-3-2-1 Go! obesity prevention program aims to change obesity risk behaviors in low-income neighborhoods in Chicago with a multilevel approach. This study follows a previous evaluation, which showed 5-4-3-2-1 Go! exposure to be associated with increased fruit and vegetable consumption. The authors examined whether increased positive beliefs about fruit and vegetable consumption were associated with exposure to program messages. Exploratory factor analysis identified a fresh fruit/vegetable availability satisfaction factor. The authors compared outcome measures between baseline and follow-up samples and between exposure and control conditions. Multivariable logistic regression models were estimated to evaluate the effects of program exposure on changes in nutrition beliefs. The study found that participants' (n = 246) beliefs about fruit and vegetable consumption were negatively associated with exposure to the program and that demographic factors, social environment, and physical environment were strongly associated with beliefs about fruit and vegetable consumption. These findings merit further research and may indicate the environmental factors that are associated with attitude formation among those reached by obesity prevention interventions, especially when many participants live in neighborhoods lacking convenient fruit and vegetable shopping options.

Effects of the above the influence brand on adolescent drug use prevention normative beliefs.

Health brands are based on the relations between individuals and health behaviors and lifestyles. Brands can be measured by the brand equity construct validated in previous studies. The National Youth Anti-Drug Media Campaign brands alternative, non-drug use behaviors as a behavior change strategy. This study goes beyond previous campaign evaluations, which did not include specific brand equity measurements. Using data from a nationally representative media tracking, this study examined the relation between antidrug campaign brand equity and adoption of targeted attitudes, beliefs, and behaviors. Data were gathered before the relaunch of the campaign, and follow-up data collected 3 months later. On the basis of factor analysis, the authors developed a higher order antidrug brand equity factor and regressed campaign outcomes on that factor in multivariable models. The authors observed significant effects of higher brand equity on higher levels of targeted antidrug attitudes and normative beliefs at follow-up. The authors also observed some counterintuitive relations (i.e., less positive attitudes at follow-up). They interpreted these results in light of the changing messages and campaign strategy. The authors conclude that antidrug brand equity is an important construct for understanding campaign effectiveness. The present campaign shows signs of changing targeted antidrug attitudes and beliefs among youth with brand equity.

Initial outcomes from a 4-week follow-up study of the Text4baby program in the military women's population: randomized controlled trial.

BACKGROUND: The use of mobile phone technologies for health promotion and disease prevention has advanced rapidly in recent years. Text4baby is a theory-based mobile health (mHealth) program in which text messages are delivered to pregnant women and new mothers to improve their health care beliefs and behaviors and improve health status and clinical outcomes. Recent evaluations of Text4baby have found that it improves targeted health attitudes and beliefs, but effects on behavior have not yet been determined. OBJECTIVE: In this study, investigators aimed to evaluate Text4baby in the military women's population. METHODS: Investigators conducted a randomized controlled trial at Madigan Army Medical Center in Tacoma, Washington, from December 2011 through September 2013. All participants were pregnant women first presenting for care at Madigan. Investigators conducted a baseline assessment using a 24-item, self-administered online survey of attitudes and behaviors related to Text4baby message content. Participants were randomized to Text4baby plus usual care (intervention) or usual care alone (control). Investigators analyzed treatment effects of Text4baby on short-term targeted outcomes 4 weeks post enrollment. RESULTS: For this study, 943 patients were randomized and completed a baseline assessment. The average patient age was 28 years and nearly 70% self-identified as Caucasian. 48.7% of enrollees (459/943) completed the first follow-up assessment. Higher rates of single and working/in-school patients dropped out of the intervention arm of the study, and we adjusted for this finding in subsequent models. However, while investigators were unable to re-survey these participants, only 1.9% of Text4baby enrollees (18/943) dropped the service during the study period. Adjusted and unadjusted logistic generalized estimating equation models were developed to assess intervention effects on measured outcomes. In the model adjusting for age, marital status, having had a previous baby, and race/ethnicity, there was a significant effect of Text4baby intervention exposure on increased agreement with belief in the importance of taking prenatal vitamins (OR 1.91, 95% CI 1.08-3.34, P=.024). All of these attitudes had been targeted by at least one text message during the 4-week evaluation period examined in this study. In unadjusted models, there was a significant effect of intervention exposure on belief in the importance of visiting a health care provider to be a healthy new mother (OR 1.52, 95% CI 1.01-2.31, P=.046) and in the health risks of alcohol during pregnancy (OR 2.06, 95% CI 1.00-4.31, P=.05). No behavioral effects of the intervention were observed in this analysis. CONCLUSIONS: Text4baby is a promising program that offers lessons for future mHealth activities. This large-scale study demonstrated initial effects of the program on attitudes and beliefs targeted by the messages received by women during the study period. Results confirm previous findings from Text4baby studies and other mHealth research. Future analyses will examine dosage effects of the intervention on behaviors and clinical outcomes.

Socioeconomic status and inequities in treatment initiation and survival among patients with cancer, 2011-2022.

BACKGROUND: Lower neighborhood socioeconomic status (SES) is associated with suboptimal cancer care and reduced survival. Most studies examining cancer inequities across area-level socioeconomic status tend to use less granular or unidimensional measures and pre-date the COVID-19 pandemic. Here, we examined the association of area-level socioeconomic status on real-world treatment initiation and overall survival among adults with 20 common cancers. METHODS: This retrospective cohort study used electronic health record-derived deidentified data (Flatiron Health Research Database, 2011-2022) linked to US Census Bureau data from the American Community Survey (2015-2019). Area-level socioeconomic status quintiles (based on a measure incorporating income, home values, rental costs, poverty, blue-collar employment, unemployment, and education information) were computed from the US population and applied to patients based on their mailing address. Associations were examined using Cox proportional hazards models adjusted for diagnosis year, age, sex, performance status, stage, and cancer type. RESULTS: This cohort included 291 419 patients (47.7% female; median age = 68 years). Patients from low-SES areas were younger and more likely to be Black (21.9% vs 3.3%) or Latinx (8.4% vs 3.0%) than those in high-SES areas. Living in low-SES areas (vs high) was associated with lower treatment rates (hazard ratio = 0.94 [95% confidence interval = 0.93 to 0.95]) and reduced survival (median real-world overall survival = 21.4 vs 29.5 months, hazard ratio = 1.20 [95% confidence interval = 1.18 to 1.22]). Treatment and survival inequities were observed in 9 and 19 cancer types, respectively. Area-level socioeconomic inequities in treatment and survival remained statistically significant in the COVID-19 era (after March 2020). CONCLUSION: To reduce inequities in cancer outcomes, efforts that target marginalized, low-socioeconomic status neighborhoods are necessary.

Perceptions of the food shopping environment are associated with greater consumption of fruits and vegetables.

OBJECTIVE: The present study examined whether characteristics such as quality, selection and convenience are associated with dietary intake of fruits and vegetables independent of perceived costs in an inner-city, low-income population. DESIGN: Secondary analysis of baseline data from a social marketing intervention designed to change household dietary practices among parents of 3- to 7-year-old children. SETTING: A community sample drawn from six low-income, primarily minority neighbourhoods in Chicago, IL, USA. SUBJECTS: From the parent study, 526 respondents completed the baseline survey and were eligible for inclusion. Of this number, 495 provided complete data on sociodemographic characteristics, fruit and vegetable consumption, perceptions of the shopping environment, perceived costs of fruits and vegetables, and food shopping habits. RESULTS: Logistic regression analysis showed that more positive perceptions of the food shopping environment were associated with greater consumption of fruits and vegetables. There was an increase of approximately twofold in the likelihood of consuming three or more fruits and vegetables daily per level of satisfaction ascribed to the shopping environment. This association was independent of perceived cost, store type and sociodemographic characteristics. CONCLUSIONS: Our data show that among a generally minority and low-income population, quality, selection and convenience are important determinants of fruit and vegetable consumption. Nutrition promotion campaigns that aim to alter the built environment by increasing access to fruits and vegetables should recognize that simply increasing availability may not yield beneficial change when characteristics of the shopping context are ignored.

Pilot evaluation of the text4baby mobile health program.

BACKGROUND: Mobile phone technologies for health promotion and disease prevention have evolved rapidly, but few studies have tested the efficacy of mobile health in full-fledged programs. Text4baby is an example of mobile health based on behavioral theory, and it delivers text messages to traditionally underserved pregnant women and new mothers to change their health, health care beliefs, practices, and behaviors in order to improve clinical outcomes. The purpose of this pilot evaluation study is to assess the efficacy of this text messaging campaign. METHODS: We conducted a randomized pilot evaluation study. All participants were pregnant women first presenting for care at the Fairfax County, Virginia Health Department. We randomized participants to enroll in text4baby and receive usual health care (intervention), or continue simply to receive usual care (control). We then conducted a 24-item survey by telephone of attitudes and behaviors related to text4baby. We surveyed participants at baseline, before text4baby was delivered to the intervention group, and at follow-up at approximately 28 weeks of baby's gestational age. RESULTS: We completed 123 baseline interviews in English and in Spanish. Overall, the sample was predominantly of Hispanic origin (79.7%) with an average age of 27.6 years. We completed 90 follow-up interviews, and achieved a 73% retention rate. We used a logistic generalized estimating equation model to evaluate intervention effects on measured outcomes. We found a significant effect of text4baby intervention exposure on increased agreement with the attitude statement "I am prepared to be a new mother" (OR = 2.73, CI = 1.04, 7.18, p = 0.042) between baseline and follow-up. For those who had attained a high school education or greater, we observed a significantly higher overall agreement to attitudes against alcohol consumption during pregnancy (OR = 2.80, CI = 1.13, 6.90, p = 0.026). We also observed a significant improvement of attitudes toward alcohol consumption from baseline to follow-up (OR = 3.57, CI = 1.13 - 11.24, p = 0.029). CONCLUSIONS: This pilot study is the first randomized evaluation of text4baby. It is a promising program in that exposure to the text messages was associated with changes in specific beliefs targeted by the messages.

Accounting for Delayed Entry in Analyses of Overall Survival in Clinico-Genomic Databases.

BACKGROUND: Clinico-genomic databases favor inclusion of long-term survivors, leading to potentially biased overall survival (OS) analyses. Risk set adjustments relying on the independent delayed entry assumption may mitigate this bias. We aimed to determine whether this assumption is satisfied in a dataset of patients with advanced non-small cell lung cancer (aNSCLC), and to give guidance for clinico-genomic OS analyses when the assumption is not satisfied. METHODS: We analyzed the association of timing of next-generation sequencing (NGS) testing with real-world OS (rwOS) in patient data from a United States-based nationwide longitudinal deidentified electronic health records-derived database. Estimates of rwOS using risk set adjustment were compared with estimates computed with respect to all patients, regardless of NGS testing. RESULTS: The independent delayed entry assumption was not satisfied in this database, and later sequencing had a negative association with the hazard of death after sequencing. In a model adjusted for relevant characteristics, each month delay in sequencing was associated with a 2% increase in the hazard of death. However, until the median survival time, estimates of OS using risk set adjustment are similar to estimates computed for all patients, regardless of NGS testing. CONCLUSIONS: rwOS analyses in clinico-genomic databases should assess the independent delayed entry assumption. Comparisons versus broader population may be useful to evaluate the rwOS differences between calculations using risk set adjustment and patient cohorts where the bias relates to overrepresentation of long survivors. IMPACT: This study illustrates practices that can increase the interpretability of findings from OS analyses in clinico-genomic databases.

ERBB2 Copy Number as a Quantitative Biomarker for Real-World Outcomes to Anti-Human Epidermal Growth Factor Receptor 2 Therapy in Advanced Gastroesophageal Adenocarcinoma.

PURPOSE: Human epidermal growth factor receptor 2 (HER2) overexpression or amplification (ERBB2amp) are biomarkers for approved anti-HER2 therapies. ERBB2amp may better predict response compared with immunohistochemistry or in situ hybridization, and quantitative copy number (CN) may further stratify patients. We characterized ERBB2amp in advanced gastroesophageal adenocarcinomas (GEA) and hypothesized that increased CN was associated with better outcome to trastuzumab. METHODS: Comprehensive genomic profiling, including assessment of ERBB2amp, was performed for 12,905 GEA tissue cases. Clinical outcomes were assessed using a clinicogenomic database linking deidentified electronic health record-derived clinical data to genomic data. Multivariable Cox proportional hazard models were used for real-world progression-free survival (rwPFS) comparisons. RESULTS: ERBB2amp (CN ≥ 5) was detected in 15% (1,934 of 12,905) of GEA; median CN 22 (interquartile range 9-73). Median ERBB2 amplicon size was 0.27 megabase (interquartile range 0.13-0.95), and smaller amplicons were associated with higher CN (P < .001). In the clinicogenomic database, of 101 evaluable first-line trastuzumab-treated patients, ERBB2 CN was a significant predictor of rwPFS as a continuous variable (adjusted hazard ratio = 0.73; 95% CI, 0.60 to 0.89; P = .002), whereas ERBB2 CN was not predictive of rwPFS on chemotherapy (adjusted hazard ratio = 0.93; 95% CI, 0.73 to 1.20; P = .59). Among trastuzumab-treated patients, no significant associations with ERBB2 CN were observed for disease site, age, stage at advanced diagnosis, or most selected coalterations. CONCLUSION: ERBB2amp was detected in 15% of GEA tissue samples, with significant diversity in ERBB2 CN and amplicon focality. ERBB2 CN was predictive of rwPFS as a continuous variable for patients treated with trastuzumab. Further studies exploring the clinical utility of quantitative ERBB2 CN, particularly in the setting of the evolving anti-HER2 landscape and combination therapies, are warranted.

Natural History of Human Epidermal Growth Factor Receptor 2-Amplified and Human Epidermal Growth Factor Receptor 2 Wild-Type Refractory Metastatic Colorectal Cancer in US Clinical Practice.

PURPOSE: The molecular heterogeneity of metastatic colorectal cancer (mCRC) presents a therapeutic challenge, with few trials focused on patients with human epidermal growth factor receptor 2 amplification (HER2-Amp). Our limited understanding of real-world patterns and outcomes by HER2 status of treatment-refractory patients leaves treatment decisions with little contextual information. We conducted a retrospective cohort study to describe the natural disease history of patients with refractory mCRC using an electronic health record-derived database with oncogenomic information. METHODS: We included patients with stage IV or recurrent mCRC diagnosed from January 2011 through December 2019 from a deidentified clinicogenomic database. Patients with ≥ 2 documented clinic visits, ≥ 2 lines of therapy (LOT) after mCRC diagnosis, and comprehensive genomic profiling were eligible. Patient records defined by treatment-refractory LOT were allocated to the HER2-Amp or HER2 wild-type (WT) cohort on the basis of comprehensive genomic profiling. Index date was defined as the start of any treatment-refractory LOT (≥ 2 LOT; patients could contribute multiple records). Descriptive statistics included demographic and clinical characteristics, treatments, laboratory values, and biomarkers. Overall survival (OS) was calculated as time (in months) from the index date until death from any cause and analyzed using Kaplan-Meier methodology. Sensitivity analyses were conducted to test the robustness of the primary findings. RESULTS: A total of 576 patients were included (1,339 records); 63 (158 records) were HER2-Amp, and 513 (1,181 records) were HER2-WT. Demographics, clinical characteristics, biomarkers, and laboratory values were comparable between HER2 cohorts. OS was similar, with an unadjusted median OS of 11.2 months (95% CI, 8.6 to 15.1) and 9.9 months (95% CI, 8.3 to 10.9) across LOT for HER2-Amp and HER2-WT cohorts, respectively. CONCLUSION: This study showed considerable treatment heterogeneity and poor outcomes among patients with treatment-refractory mCRC, emphasizing a substantial unmet therapeutic need.

Assessing public and private sector contributions in reproductive health financing and utilization for six sub-Saharan African countries.

The present study provides evidence to support enhanced attention to reproductive health and comprehensive measures to increase access to quality reproductive health services. We compare and contrast the financing and utilization of reproductive health services in six sub-Saharan African countries using data from National Health Accounts and Demographic and Health Surveys. Spending on reproductive health in 2006 ranged from US$4 per woman of reproductive age in Ethiopia to US$17 in Uganda. These are below the necessary level for assuring adequate services given that an internationally recommended spending level for family planning alone was US$16 for 2006. Moreover, reproductive health spending shows signs of decline in tandem with insufficient improvement in service utilization. Public providers played a predominant role in antenatal and delivery care for institutional births, but home deliveries with unqualified attendants dominated. The private sector was a major supplier of condoms, oral pills and IUDs. Private clinics, pharmacies and drug vendors were important sources of STI treatment. The findings highlight the need to commit greatly increased funding for reproductive health services as well as more policy attention to the contribution of public, private and informal providers and the role of collaboration among them to expand access to services for under-served populations.

Brand equity and willingness to pay for condoms in Zimbabwe.

BACKGROUND: Zimbabwe suffers from one of the greatest burdens of HIV/AIDS in the world that has been compounded by social and economic instability in the past decade. However, from 2001 to 2009 HIV prevalence among 15-49 year olds declined from 26% to approximately 14%. Behavior change and condom use may in part explain this decline.PSI-Zimbabwe socially markets the Protector Plus (P+) branded line of condoms. When Zimbabwe converted to a dollar-based economy in 2009, the price of condoms was greatly increased and new marketing efforts were undertaken. This paper evaluates the role of condom marketing, a multi-dimensional scale of brand peceptions (brand equity), and price in condom use behavior. METHODS: We randomly sampled sexually active men age 15-49 from 3 groups - current P+ users, former users, and free condom users. We compared their brand equity and willingness to pay based on survey results. We estimated multivariable logistic regression models to compare the 3 groups. RESULTS: We found that the brand equity scale was positive correlated with willingness to pay and with condom use. Former users also indicated a high willingness to pay for condoms. We found differences in brand equity between the 3 groups, with current P+ users having the highest P+ brand equity. As observed in previous studies, higher brand equity was associated with more of the targeted health behavior, in this case and more consistent condom use. CONCLUSIONS: Zimbabwe men have highly positive brand perceptions of P+. There is an opportunity to grow the total condom market in Zimbabwe by increasing brand equity across user groups. Some former users may resume using condoms through more effective marketing. Some free users may be willing to pay for condoms. Achieving these objectives will expand the total condom market and reduce HIV risk behaviors.

TRK Fusion Cancer: Patient Characteristics and Survival Analysis in the Real-World Setting.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers in various tumor types. While NTRK gene fusions are predictive of benefit from tropomyosin receptor kinase inhibitors regardless of tumor type, the prognostic significance of NTRK gene fusions in a pan-tumor setting remains unclear. OBJECTIVE: This study evaluated the characteristics and prognosis of tropomyosin receptor kinase fusion cancer in the real-world setting. PATIENTS AND METHODS: This retrospective study used a de-identified clinico-genomic database and included patients with cancer who had comprehensive genomic profiling between January 2011 and July 2018. Patients were classified as having cancer with NTRK gene fusions or NTRK wild-type genes. Patients were matched with a 1:4 ratio (NTRK fusion:NTRK wild-type) using the Mahalanobis distance method on demographic and clinical characteristics, including age and Eastern Cooperative Oncology Group performance status. Descriptive analysis of clinical and molecular characteristics was conducted. Kaplan-Meier estimator and Cox regression were used for overall survival analysis. RESULTS: Median overall survival was 12.5 months (95% confidence interval 9.5-not estimable) and 16.5 months (95% confidence interval 12.5-22.5) in the NTRK gene fusion (n = 27) and NTRK wild-type cohorts (n = 107), respectively (hazard ratio 1.44; 95% confidence interval 0.61-3.37; p = 0.648). Co-occurrence of select targetable biomarkers including ALK, BRAF, ERBB2, EGFR, ROS1, and KRAS was lower in cancers with NTRK gene fusions than in NTRK wild-type cancers. CONCLUSIONS: Although the hazard ratio for overall survival suggested a higher risk of death for patients with NTRK gene fusions, the difference was not statistically significant. Co-occurrence of NTRK gene fusions and other actionable biomarkers was uncommon.

Retrospective analysis of real-world data to determine clinical outcomes of patients with advanced non-small cell lung cancer following cell-free circulating tumor DNA genomic profiling.

OBJECTIVES: Liquid biopsy and comprehensive genomic profiling (CGP) of circulating tumor DNA (ctDNA) are increasingly used for detection of targetable genomic alterations (GA) in non-small cell lung cancer (NSCLC). To examine the clinical outcomes for patients following CGP using liquid biopsy versus tissue biopsy, receipt of matched targeted therapy post-CGP and associated outcomes were evaluated in the real-world setting. METHODS: 6491 patients with NSCLC and liquid biopsy (N = 937 tests) and/or tissue (N = 5582 tests) CGP were included in a de-identified commercial clinico-genomic database. Targetable GAs included National Comprehensive Cancer Network NSCLC guideline biomarkers. Clinical characteristics, real-world progression, and real-world response (rwR) were obtained via technology-enabled abstraction of clinician notes and radiology/pathology reports. RESULTS: At the time of liquid biopsy CGP, 53% (496/937) of patients were documented to have received ≥1 line of prior therapy (tissue CGP: 13%, 735/5582). 90% (832/928) of liquid biopsy cases had evidence of ctDNA. A targetable GA was detected in 20% (188/937) of liquid biopsy and 22% (1215/5582) of tissue CGP cases. Use of matched targeted therapy overall was similar post-liquid biopsy or post-tissue CGP but varied considerably across emerging (25%, 79/317) versus standard of care (SOC) (74%, 475/640) GA. Real-world-progression free survival for patients receiving SOC first line matched targeted therapy administered following liquid biopsy (n = 33) and tissue (n = 229) CGP were similar (13.8 vs 10.6 months; aHR = 0.68 [0.36-1.26]). Among patients evaluated for rwR, overall response rate (partial/complete response) to matched targeted therapy post-liquid biopsy CGP was 75% (39/52) versus 66% post-tissue CGP (254/385, P = 0.51). CONCLUSION: Retrospective analysis of real-world clinico-genomic data demonstrated that clinical outcomes on matched targeted therapy were similar following liquid biopsy and tissue CGP in NSCLC, which suggests routine clinical use of liquid biopsy CGP can reliably guide therapy selection.

Comparison of Treatment, Cost, and Survival in Patients With Metastatic Colorectal Cancer in Western Washington, United States, and British Columbia, Canada.

PURPOSE: Few studies have directly compared health care utilization, costs, and outcomes between patients treated in the US multipayer health system and Canada's single-payer system. Using cancer registry and claims data, we assessed treatment types, costs, and survival for patients with metastatic colorectal cancer (mCRC) in Western Washington State (WW) and British Columbia (BC). MATERIALS AND METHODS: Patients age ≥ 18 years diagnosed with mCRC in 2010 and later were identified from the BC Cancer database and a regional database linking WW SEER to claims from Medicare and two large commercial insurers. Demographics, treatment characteristics, costs of systemic therapy, and survival data were obtained from these databases and compared between the two regions. RESULTS: A total of 1,592 patients from BC and 901 from WW were included in the study. Median age was similar (BC, 66 years; WW, 63 years), but patients in BC were more likely to be male (57.1% v 51.2%; P ≤ .01) and to have de novo metastatic disease (61.0% v 38.3%; P ≤ .01). The use of radiation therapy was similar between regions (BC, 31.2%; WW, 33.9%; P = .18), but primary tumor resection was more common in BC (74.1% v 66.3%; P ≤ .01) as was hepatic metastasectomy (12.4% v 2.3%; P ≤ .01). Similar percentages of patients received systemic therapy (BC, 68.8%; WW, 67.1%; P = .40), but costs were significantly higher for first-line systemic therapy in WW ($6,226 v $15,792 per patient per month; P ≤ .01). Median overall survival was similar (BC, 16.9 months; WW, 18 months). CONCLUSION: Cost of systemic therapy for mCRC was significantly higher for patients in WW than in BC, but this did not translate to a difference in overall survival.