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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.

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.

BackgroundThe Flatiron Health-Foundation Medicine Clinico-Genomic Databases (CGDBs) are de-identified, real-world data sources that link comprehensive genomic profiling (CGP) data with clinical data derived from electronic health records (EHRs) for patients with cancer. Comparing the CGDBs to the US population of patients with cancer allows researchers to understand the representativeness of a cohort when designing, conducting, and interpreting their analyses. The objective of this study was to compare the demographic and clinical characteristics of patients in the CGDBs with the Flatiron Health Research Databases (FHRDs) and The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) population-based cancer registry.MethodsWe compared disease-specific CGDBs that had corresponding disease-specific FHRDs with relevant SEER patients using demographic and clinical characteristics of patients with cancer who had documented care from January 1, 2011 to March 31, 2021. For CGDBs where a corresponding disease-specific FHRD does not exist, comparisons were only done against SEER. The SEER Incidence Data 1975-2018 Research Database was used for this analysis, of which patients with a relevant cancer diagnosis from January 1, 2011 to December 31, 2018 were included. Subgroup analyses were performed to address potential biases related to temporal drifts and allow for a more direct comparison of the datasets as well as to examine biases that may be due to data missingness. The impact of the determination to reimburse for next generation sequencing (NGS) testing was not feasible to analyze given the most recent SEER data was available only through the end of 2018 at the time this study was conducted.ResultsThe overall distribution of cancer types was similar between the 22 CGDB databases and SEER. The overall distributions of gender and diagnosis year were similar across all databases. The CGDB has a lower proportion of patients who were aged 80 years or older at initial diagnosis compared to FHRD and SEER cohorts. However, narrower differences were observed in diseases where targeted therapies are approved and comprehensive genomic profiling is indicated (e.g., Melanoma, NSCLC). The proportion of incomplete records for race in the CGDB and FHRD was greater than in SEER. Completeness of stage varied by disease across all 3 cohorts, but was generally lower in CGDB and FHRD for clinical and data model design reasons. Overall the stage distributions for solid tumor cohorts were similar across CGDB and FHRD with SEER tending to have more earlier stage patients, which is expected given differences in data collection methods for the sources.ConclusionThis comparative analysis of real-world, US-based oncology databases provides crucial insights into the similarities and differences in patient characteristics across these three types of data sources. Observed variances could be due to several factors, including differences in CGP testing dynamics and data collection approaches used to create each of the databases. Ongoing monitoring and evaluation of the representativeness of these databases will be critical to help researchers and regulators contextualize evidence from the CGDBs, particularly as the CGDBs are expected to change over time due to increased adoption of CGP as part of routine clinical practice for a growing number of cancers.

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. Supplementary Information The online version contains supplementary material available at 10.1007/s11523-021-00815-4.

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., ERBB2 copy number is a quantitative biomarker for outcomes to anti-HER2 therapy in advanced gastroesophageal cancer.

Background Small cell lung cancer (SCLC) has the strongest association with smoking among lung cancers. The characteristics of never smokers with SCLC is not known. Research Question Are the clinical characteristics, prognostic factors, survival, genomic alterations, and tumor mutational burdens of SCLC in patients who have never smoked different from those who have smoked? Study Design and Methods A retrospective multicenter cohort study of patients with clinician-confirmed SCLC was performed with the use of a longitudinal and nationally representative electronic medical records database. Smoking history was assessed through technology-enabled abstraction and confirmed for never smokers via chart review. Genomic characteristics of never smoker patients with SCLC were examined with the use of a next-generation sequencing-based gene panel and whole exome sequencing. Results One hundred of 5,632 patients (1.8%) with SCLC were never smokers. Relative to smokers, never smokers were more likely to be female (66.0% vs 52.4%; P = .009) and present with extensive stage (70.0% vs 62.2%; P = .028). Never smokers had a higher proportion of patients in age groups 35 to 49 years (7.0% vs 3.0%; P = .006) and ≥80 years (17.0% vs 8.2%; P = .006). Known risk factors for lung cancer were found in Interpretation The sex- and age-specific distribution of SCLC among never smokers, along with differences that were identified by genomic analyses, suggests a distinct biology of SCLC in never smokers compared with smokers.

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.

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.

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

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.

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.

Introduction: While lower socioeconomic status (SES) is associated with worse cancer outcomes, most electronic health records (EHRs) lack documentation of SES. Here we apply an area-level SES measure to an EHR-derived database to evaluate representativeness according to SES. We then examine socioeconomic disparities in the timeliness of healthcare utilization (biomarker testing and systemic treatment) and overall survival (OS) in 3 common cancers. Methods: This retrospective study uses the nationwide Flatiron Health EHR-derived de-identified database of cancer patients who have clinical activity between January 2011-August 2021. Census block group data from the American Community Survey (2015-2019) was used to measure SES per the Yost Index (incorporating income, home values, rental costs, poverty, blue-collar employment, unemployment, and education information). SES quintiles were determined from the US population and then applied to patients based on their residential addresses. Our database included 2,067,644 cancer patients from community practices. Patients with advanced non-small-cell lung cancer (aNSCLC, n=51,596), metastatic breast cancer (mBC, n=18,268), and multiple myeloma (MM, n=8,246) were sampled and followed from advanced, metastatic, or initial diagnosis date, respectively. Differences were evaluated using Χ2 tests for categorical variables and log-rank tests for Kaplan-Meier survivor functions. Results: Compared to the US population, our database of cancer patients has a similar SES distribution (differences Conclusion: Lower SES was associated with reduced clinical trial participation, less timely healthcare utilization, and worse OS. Making SES available in real-world data can support the development of inclusive clinical trials and inform interventions to reduce cancer care disparities. Citation Format: Jenny S. Guadamuz, Xiaoliang Wang, Jeremy Snider, James Walters, Rebecca A. Miksad, Gregory S. Calip. Socioeconomic disparities in healthcare utilization and overall survival among patients with cancer: Application of area-level socioeconomic status in a nationwide electronic health record-derived database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3668.

9045 Background: ICPI are compelling therapies for pts with aNSCLC given the potential for durable benefit and limited toxicity. Even in tumors with biomarkers associated with ICPI response, early progression (eP) can be seen, leading to chemotherapy combination approaches. We hypothesize that ctDNA tumor fraction (TF) may identify pts at risk of eP on ICPI, helping to select the optimal first-line regimen. Methods: This study used the nationwide (US-based) de-identified Flatiron Health-Foundation Medicine NSCLC clinico-genomic database (FH-FMI CGDB). The de-identified data originated from ~280 US cancer clinics (~800 sites of care). Real-world overall survival (rwOS) accounting for delayed entry and real-world progression free survival (rwPFS) were estimated with Kaplan-Meier analysis. Hazard ratios (HR) were calculated using multivariate Cox proportional hazard models adjusting for relevant covariates. TF was calculated using an aneuploidy-based measure plus variant-based estimate and was categorized as follows: ≥10%: elevated, 1-10%: intermediate, < 1%: low. eP was defined as rw progression within 8 weeks of starting therapy. Results: 426 pts with documented aNSCLC initiated 1st or 2nd line ICPI (128 ICPI, 298 ICPI+chemo) within 60 days of liquid biopsy. 88 (21%) pts had elevated TF, 193 (45%) had intermediate, and 145 (34%) had low. Pts with elevated TF had higher frequency of liver involvement (elevated: 27%; intermediate: 12%; low: 8%) and had worse performance status (ECOG 2+) near the start of therapy (elevated: 33%; intermediate 22%; low: 17%). PD-L1 was unknown for most pts (elevated: 44%; intermediate: 53%; low: 57%); elevated TF was associated with high PD-L1 positivity (elevated: 22%; intermediate: 17%; low: 12%). In pts with elevated TF, eP was more frequent (elevated: 26%, intermediate: 22%, low: 15%). Amongst all patients treated with either ICPI ± chemo, low TF was associated with better median rwPFS (low 6.7m [ref]; intermediate 5.1m, HR: 1.39 [1.11-1.74]; elevated 3.4m, HR: 1.74 [1.31-2.31]) and median rwOS: (low 14.2m [ref]; intermediate 8.4m, HR: 1.52 [1.10-2.09]; elevated 4.6m, HR: 2.17 [1.47-3.21]). In pts with elevated TF, the addition of chemo to ICPI was associated with favorable rwPFS and rwOS compared to pts who received ICPI alone (Table). Conclusions: ctDNA TF identifies pts with aNSCLC with an increased risk of eP on ICPI who may benefit from ICPI+chemo. In pts with low TF, outcomes on ICPI alone are favorable and similar to those receiving ICPI+chemo, suggesting low TF may be a non-invasive tool for identifying pts for single-agent ICPI. [Table: see text]

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.

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.

This paperg 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 pro-violence and increased anti-violence 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 anti-violence 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.

Since 2000, the truth campaign has grown as a social marketing brand. Back then, truth employed branding to compete directly with the tobacco industry. In 2014, the launch of truth FinishIt reflected changes in the brand's strategy, the tobacco control environment, and youth/young adult behavior. Building on a previous validation study, the current study examined brand equity in truth FinishIt, as measured by validated multi-dimensional scales, and tobacco related attitudes, beliefs, and behavior based on two waves of the Truth Longitudinal Cohort data from 2015 and 2016. A fixed effects logistic regression was used to estimate the change in brand equity between panel survey waves 3 and 4 on past 30-day smoking among ever and current smokers. Additional models determined the effects of brand equity predicting tobacco attitudes/use at follow up among the full sample. All analyses controlled for demographic factors. A one-point increase in the brand equity scale between the two waves was associated with a 66% greater chance of not smoking among ever smokers (OR 1.66, CI 1.11–2.48, p, Highlights • The truth FinishIt brand reflects changes in the tobacco control environment. • Brand equity mediates FinishIt exposure and tobacco use outcomes. • An increase in brand equity over 6 months was associated with lower smoking. • Higher brand equity at an earlier time predicted less smoking after 6 months. • Branding is an effective strategy in tobacco control and should be optimized.

BACKGROUND: Small cell lung cancer (SCLC) has the strongest association with smoking among lung cancers. The characteristics of never smokers with SCLC is not known. RESEARCH QUESTION: Are the clinical characteristics, prognostic factors, survival, genomic alterations, and tumor mutational burdens of SCLC in patients who have never smoked different from those who have smoked? STUDY DESIGN AND METHODS: A retrospective multicenter cohort study of patients with clinician-confirmed SCLC was performed with the use of a longitudinal and nationally representative electronic medical records database. Smoking history was assessed through technology-enabled abstraction and confirmed for never smokers via chart review. Genomic characteristics of never smoker patients with SCLC were examined with the use of a next-generation sequencing-based gene panel and whole exome sequencing. RESULTS: One hundred of 5,632 patients (1.8%) with SCLC were never smokers. Relative to smokers, never smokers were more likely to be female (66.0% vs 52.4%; P = .009) and present with extensive stage (70.0% vs 62.2%; P = .028). Never smokers had a higher proportion of patients in age groups 35 to 49 years (7.0% vs 3.0%; P = .006) and ≥80 years (17.0% vs 8.2%; P = .006). Known risk factors for lung cancer were found in

PurposeThe overall goal of the Saleema Initiative in Sudan is to promote long-term abandonment of female genital mutilation and cutting (FGM) through a contribution to changing social norms, attitudes, and intentions related to the practice. The initiative aims to create positive cultural associations with a girl remaining uncut, a new social norm. Saleema hypothesizes that branding the alternative to FGM (abandonment) will promote social norms change. In 2014, the lead author designed a monitoring and evaluation framework for Saleema in partnership with UNICEF, the National Council for Child Welfare (NCCW), and local organizations.MethodsThe Saleema evaluation aimed to evaluate the effectiveness of the campaign in reducing pro-FGM social norms. A quasi-experimental design controlled for dosage of campaign messages delivered across the 18 states in Sudan to measure a dose-response effect. We operationalized social norms through a 4-item scale validated in previous research.ResultsThis paper reports on quantitative evaluation findings based on data gathered in from 2015-2017 and focuses on the dose-response relationship between Saleema exposure and changes in FGM social norms. We found that self-reported exposure was associated with reduced pro-FGM social norms (coeff. = -0.329, p < .001). Additionally, higher doses of Saleema, measured through an exogenous measure of campaign event exposure from an independent monitoring system was associated with reduced pro-FGM social norms (coeff. = -0.146, p < .001).ConclusionsSaleema was effective in reducing pro-FGM social norms. It is a promising strategy and findings contribute to the growing literature on social norms approaches to behavior change.

Background: Four-fold growth in the past decade of actionable molecular targets for aNSCLC makes comprehensive assessment of pts' alteration status increasingly important. NGS can concurrently detect multiple genomic alterations and provides key insights to guide therapy selection. This study examined real-world NGS testing patterns and characteristics of pts with aNSCLC over time using three real-world databases (DB). Methods: Pts diagnosed (dxed) with stage IIIB/C or IV NSCLC were selected from 1) Flatiron Health (FH) nationwide (US-based) de-identified EHR-derived clinical DB (FHDB); 2) FH-Foundation Medicine (FMI) clinico-genomic DB (CGDB), which includes FH clinical data linked to genomic data for pts tested by FMI, 3) Surveillance, Epidemiology and End-Results (SEER) US population-based cancer registry. Baseline characteristics were compared for pts included in each DB diagnosed in 2012-13, 2014-15 and 2016-17. Additional features and NGS test use were compared for pts in CGDB vs FHDB dxed in 2018-19. Changes in NGS test use over time were evaluated with Chi-squared tests for trend. Results: Percent of NGS-tested pts in FHDB increased from 5% (366/7768) in 2012-2013 to 35% (3460/9759) in 2018-2019 (p Conclusions: NGS testing increased markedly and moved earlier in the treatment course over time, aligned with the growth in molecular targets. These findings show that pts who are NGS-tested have become more reflective of the general aNSCLC population, and suggest that real-world NGS use largely captures the aNSCLC genomic landscape. Table. Pt characteristics over time in NGS-tested (CGDB) vs overall aNSCLC populations (FHDB, SEER)CharacteristicaNSCLC Diagnosis Year2012-132014-152016-172018-19Number of Pts289107817842327CGDB289107817842327FHDB77689989103319759SEER378123781036874n/a*65 yrs or older at aNSCLC diagnosisCGDB42%53%60%64%FHDB64%64%66%67%SEER61%62%64%n/a*FemaleCGDB53%51%49%48%FHDB46%46%46%46%SEER44%45%46%n/a*Non-squamous cell histologyCGDB81%82%77%75%FHDB70%72%71%71%SEER66%69%69%n/aCommunity-based practiceCGDB89%94%93%93%FHDB92%91%91%90%History of SmokingCGDB72%79%80%84%FHDB86%86%86%87%*SEER data are available only through 2017, and do not include information on practice setting or smoking history Citation Format: Akshay Swaminathan, Stella Stergiopoulos, Jeremy Snider, Virginia Fisher, Emily Castellanos, Tamara Snow, Cheryl Cho-Phan, Leah Comment, Rachel Cunningham, Margaret E. McCusker. Changes over time in real-world next-generation sequencing (NGS) test use in patients (pts) with advanced non-small cell lung cancer (aNSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 864.

4045 Background: HER2 ( ERBB2) overexpression or amplification (amp) are biomarkers for approved anti-HER2 therapies. ERBB2amp may be a superior predictor of anti-HER2 therapy outcome compared to IHC/ISH, and degree of CN gain may further stratify patients (pts). We investigated the distribution of ERBB2amp in adv GEA and hypothesized that increased CN was associated with better outcome to trastuzumab (T). Methods: Genomic analysis was performed using the Foundation Medicine (FM) tissue database (DB) of 313,896 pts with solid tumors including 12,749 pts with GEA and 34,629 pts with breast cancer (BC) used for comparison. ERBB2amp was defined as predicted CN ≥5 with > 80% of exons amplified. Using the nationwide US-based Flatiron Health-FM clinico-genomic DB linking de-identified EHR-derived clinical data to FM genomic data, pts with ERBB2amp adv GEA (01/2011 - 12/2020) were selected. RW progression (rwP) was obtained via technology-enabled abstraction of EHR. Multivariable Cox proportional hazard models were used for outcome comparisons. Results: ERBB2amp was detected in 15% (1,920/12,749) of GEA samples; median CN 22 (IQR 9-73), and 97% of cases had full gene amp. Median ERBB2 amplicon size was 0.27Mbp (IQR 0.13-0.95). In comparison, ERBB2amp was detected in 9.2% (3,193/34,629) of BC samples; median CN 20 (IQR 9-40), median amplicon size 0.32Mbp (IQR 0.13-1.37). In both cancers, smaller amplicons were associated with higher CN (P < 0.001), excluding amplicons < 0.1Mbp where less than 100% target amp was common. ERBB2amp was additionally seen in 2.7% of other solid tumors, and specifically in 2.3% of NSCLC and 3.1% of CRC. In the RW DB of 183 pts with ERBB2amp adv GEA, chemo + T (45%) and chemo alone (17%) were the most common first therapies after genomic report. In 101 evaluable first-line T treated pts ERBB2 CN was a significant predictor of rwP free survival (rwPFS) as a continuous variable (aHR = 0.74 [95% CI: 0.61 - 0.89], P = 0.002) and a range of cutoffs were similarly predictive. For control, in ERBB2amp pts treated with chemo ERBB2 CN was not predictive of rwPFS (aHR = 0.93, [95% CI: 0.72 – 1.20], P = 0.060). Among T treated pts, co- PIK3CA mutation was more common with lower CN (p = 0.03 by Wilcox test); no significant differences were observed for primary tumor location, age, stage at adv diagnosis, co- KRASmut, EGFRamp or F GF R1/2amp. Conclusions: ERBB2amp was detected in 15% of GEA tissue samples, with significant diversity in ERBB2 CN and amplicon focality, but with a similar CN distribution and amplicon focality seen in ERBB2amp BC. ERBB2 CN was predictive of rwPFS as a continuous variable for pts with GEA treated with T in the RW setting. Further studies exploring the clinical utility of quantitative ERBB2 CN, and extending to ctDNA, particularly in the setting of the evolving anti-HER2 landscape and combination therapies, are warranted.

1036 Background: HER2 overexpression/amplification measured by IHC or ISH is a predictive biomarker for HER2-targeted therapies. Next-generation sequencing (NGS) can identify ERBB2 amplification (amp) and mutations. We examined clinical characteristics, NGS testing patterns, and outcomes of pts treated with 1L HER2 therapy with HER2+ mBC based on ERBB2 amp status using a real-world (RW) clinico-genomic database (CGDB). Methods: Pts with mBC (HER2+ by IHC and/or ISH) treated with 1L HER2 therapy who had undergone NGS and were treated within the Flatiron Health (FH) network were eligible. Clinical characteristics and HER2 testing results were obtained via technology-enabled abstraction of clinician notes and radiology/pathology reports and linked to genomic data from Foundation Medicine (FMI) in the nationwide (US-based), de-identified FH-FMI CGDB. Demographic, clinical and genomic characteristics were summarized and stratified by concordance between HER2+ (IHC 3+ or ISH amp+) and ERBB2amp+ status [copy number (CN) ≥ 5]. NGS testing patterns and 1L HER2 therapy were characterized and stratified by concordance status. Concordance was assessed based on contemporaneous timing of paired test specimen collection dates (FMI NGS ≤ 30 days of HER2+ status). RW overall survival (rwOS) stratified by HER2+/ ERBB2 amp concordance was estimated with Kaplan-Meier analysis and adjusted Cox proportional hazards models. Results: Among 268 eligible pts, HER2+/ ERBB2amp+ concordance was 66% (176/268); concordance among contemporaneous paired specimens was 73% (106/145). Demographic and clinical features were overall well-balanced with most pts treated at community sites [94%, (252/268)]; the discordant (HER2+/ ERBB2amp-) group (95/268) had more pts with hormone receptor positive disease (73% vs 62%). Concordance by assay type varied; IHC+ only, IHC+/ISH+, and ISH+ only agreement was 72% (95/132), 76% (26/34) and 52% (50/96), respectively. A higher proportion of discordance (35% vs 19%) was seen in pts treated at community vs. academic sites. Median rwOS was 32.9 months (IQR 25.9-38.9) among concordant (HER2+/ ERBB2amp+) and 15.5 months (IQR 8.9-30.1) among discordant (HER2+/ ERBB2amp-) pts, aHR = 0.71 [95% CI: 0.48-1.03; p = 0.073]. Conclusions: Among RW pts with HER2+ mBC receiving 1L HER2 therapy, discordance between ERBB2amp and IHC/ISH HER2 testing methods was observed. Pts with tumors HER2+ by IHC and/or ISH but negative for ERBB2amp had a trend towards worse rwOS following receipt of HER2 therapy compared to concordant cases. Contemporaneous timing of specimen collection was associated with greater concordance. Future analyses on the additive value of ERBB2 CN as a predictive marker, and assessing factors that may affect discordance such as intratumor HER2 heterogeneity, tumor content, and biopsy site are warranted.

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.

Introduction: The neurotrophic tyrosine receptor kinase (NTRK) genes NTRK1, 2, and 3 have emerged as oncogenic drivers, and their resultant tropomyosin receptor kinase (TRK) proteins are targets for precision medicines. Larotrectinib, a selective TRK inhibitor, and entrectinib, a multikinase inhibitor, have been approved for patients (pts) with TRK fusion cancer. This study was conducted to evaluate the molecular characteristics and prognosis of TRK fusion cancer in a real-world setting. Methods: This is a retrospective study using the de-identified Flatiron Health-Foundation Medicine Clinico-Genomic Database (CGDB) that includes pts with a diagnosis of cancer who had comprehensive genomic profiling (CGP) between Jan 2011 and Jul 2018 (Version Nov. 2018). Pts were classified based on the status of their NTRK gene: cohort 1 included pts with NTRK gene fusions and cohort 2 included pts with wild-type NTRK genes (WT-TRK). Within each tumor type, matching was conducted between the two cohorts using the Mahalanobis distance method with a ratio of 1:4 (cohort 1: cohort 2) on demographic and clinical characteristics including age, albumin, antineoplastic use, ECOG performance status, practice type, and year of CGP report. Descriptive analyses were provided for patient and molecular characteristics. Kaplan-Meier method and Cox regression were used for overall survival (OS) analysis with the date of the CGP report as the index date. Results: Of 33,398 pts in the CGDB, 29 pts across 18 histologies had an NTRK gene fusion and 12,456 pts had the same histologies with WT-TRK. In pts with NTRK gene fusions, NTRK1 was involved in 18 (62.1%), NTRK2 in 3 (10.3%), and NTRK3 in 8 (27.6%) of the observed fusion events. Co-occurrence of specific biomarkers (ALK, BRAF, ERBB2, EGFR, ROS1, KRAS) was rare, and lower in pts with NTRK gene fusions than in WT-TRK pts; however, high TMB and MSI were more common in pts with NTRK gene fusions than in WT-TRK pts (TMB high 20.7% vs. 2.8% and MSI high 10.3% vs. 0.9%, respectively). 27 pts from cohort 1 were matched with 102 pts in cohort 2. Demographic and baseline clinical characteristics were generally similar between the matched cohorts. A median OS from CGP report date of 16.5 months (95% CI 11.5-22.5) was observed for the WT-TRK pts, compared with 12.5 months (95% CI 9.5—not reached) for the pts with TRK fusion cancer. The proportional hazards ratio comparing pts with TRK fusion vs. WT-TRK cancer was 1.436 (95% CI 0.612-3.373). Conclusions: Pts with TRK fusion cancer had lower co-occurrence of other oncogenic biomarkers but had higher frequencies of MSI-high and TMB-high vs. pts with WT-TRK cancer. While no clear differences in OS were seen, there was a trend to shorter OS for pts with TRK fusion cancer. Further study allowing for inclusion of additional prognostic factors is needed to confirm the prognostic value of NTRK gene fusions. Citation Format: Lyudmila Bazhenova, Xiaolong Jiao, Andrew Lokker, Jeremy Snider, Emily Castellanos, Shivani Nanda, Virginia Fisher, Jihong Zong, Karen Keating, Marc Fellous. Cancers with NTRK gene fusions: Molecular characteristics and prognosis [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 09.

9591 Background: EGFR x19dels are well-established targetable drivers in NSCLC. Historically x19dels have been treated as a single group, but it’s unclear whether responses vary for distinct subtypes. We compared demographic, clinical and genomic characteristics as well as outcomes to EGFR tyrosine kinase inhibitors (TKIs) for aNSCLC pts with x19dels of varying lengths using a RW Clinico-Genomic Database (CGDB). Methods: Eligible pts had a diagnosis of aNSCLC, received care within the Flatiron Health network between 1/2011-9/2019, and had comprehensive genomic profiling (CGP) by Foundation Medicine. Clinical characteristics, treatment history and RW progression were obtained via technology-enabled abstraction as previously described (Singal G, JAMA 2019). x19del length was evaluated for association with overall survival (OS) and RW progression-free survival (rwPFS) with Kaplan-Meier analysis and unadjusted/adjusted (practice type, gender, age at TKI start, EGFR TKI type, race) hazard ratios (HR/aHR) from Cox proportional hazards models adjusted for survival bias. Results: Among 6,577 aNSCLC pts, EGFR x19dels were detected in 336 cases (5%). E746_A750del was the most frequent (214; 64%) and generally 5 amino acid (aa) deletions (x19del-5) were the most common (241; 72%). Other deletions (x19del-other) of 6 (61; 18%), 3 (20; 6%), 4 (11; 3%) or 8 aa (3; 1%) were also observed. Among pts treated with 1st-line EGFR TKI monotherapy after CGP, the x19del-5 (n = 70) cohort was more frequently female compared to x19del-other (n = 27) (90% vs 59%, p = 0.001). No statistically significant differences in the frequency of co-occurring alterations were observed, specifically for genes associated with response to EGFR TKI response such as CTNNB1 (14% vs 19%) and PIK3CA (10% vs 15%). 1st line EGFR TKIs used were similar for x19del-5 vs x19del-other (43% vs 41% osimertinib, 30% vs 37% erlotinib, 24% vs 22% afatinib, 3% vs 0% gefitinib). x19del-5 pts had similar median rwPFS (10.6 vs 10.6 months, HR: 0.73 [0.41-1.28], aHR:0.78 [0.38-1.59]) and median OS (29.2 vs 24.9 months, HR: 0.64 [0.32- 1.29], aHR: 0.75 [0.32-1.75]) compared to x19del-other. Conclusions: In a RW CGDB of 336 aNSCLC pts with EGFR x19dels, 5 aa x19dels were most common (71%) and 29% of cases had 3, 4, 6 or 8 aa x19dels . For pts included in the treatment cohort, no significant differences in rwPFS or OS were observed. These results suggest that x19del length does not significantly impact clinical outcomes to 1st-line EGFR TKIs.

3060 Background: The first tumor-agnostic, biomarker-based FDA approval in oncology was P in May 2017 for pts with MSI-H or mismatch repair (MMR) deficient tumors. 1 yr overall survival (OS) was >70% for colorectal cancer (CRC) and >60% for non-CRC in P-treated MSI-H clinical trial pts (Le 2019; Marabelle 2019). As tumor-agnostic therapies are a new paradigm, it is important to assess their use and effectiveness in routine clinical practice. We examined characteristics and outcomes of RW pts with MSI-H solid tumors who received P after May 2017. Methods: Pts with MSI-H solid tumors who received P after May 2017 were selected from the Flatiron Health-Foundation Medicine (FH-FMI) clinico-genomic database, a nationwide de-identified EHR-derived database linked to comprehensive genomic profiling (CGP) data. Pts with 2+ visits in the FH network from 01/2011-09/2019 with CGP prior to P use were included. Clinical characteristics were assessed at first P use. Time to treatment discontinuation (TTD) and OS from first P use were estimated with Kaplan-Meier analyses of all pts and the largest tumor types. Results: 33,395 pts had a solid tumor tested for MSI by CGP, of which 557 (1.7%) were MSI-H (median age 68 yrs; 34% male). 129 MSI-H pts across 33 tumor types received first P after May 2017. CRC (N=36) and Endometrial cancer (N=39) were most common. 52 pts (40%) had a concurrent MMR alteration (MLH1, MSH2, MSH6 or PMS2); median TMB was 32.2 mut/mb (IQR 20.9-47.5). Median number of therapies prior to P was 1; median time from CGP to first P use was 3 mos. Table shows OS and TTD. Conclusions: In this RW study, P use was observed across 33 MSI-H tumor types. Median OS exceeded 1 yr across all pts and in CRC, Endometrial, and Other cohorts. 1 yr OS rate was consistent with P trial outcomes. Further study should evaluate whether effectiveness differs across diseases, MSI testing method, or other genomic attributes to improve treatment selection. [Table: see text]

5527 Background: Inactivating alts in BRCA1/2 result in homologous recombination deficiency and are predictive of PARPi response in mCRPC. BRCA reversion mutations, which restore the protein function, are frequently observed in acquired resistance to PARPi. In tumors harboring homozygous gene deletions ( BRCAdel) reversions cannot develop; thus, we hypothesize that BRCAdel pts may have prolonged benefit from PARPi compared to pts harboring other BRCA alterations. Methods: Pts were included from the Flatiron Health (FH)-Foundation Medicine (FMI) de-identified clinico-genomic database (CGDB). Inclusion criteria were diagnosis of mCRPC, treatment in the FH network and an FMI comprehensive genomic profiling result between 1/1/2011 - 9/30/2019. Time to therapy discontinuation (TTD) and overall survival (OS) from start of PARPi were estimated with Kaplan-Meier analysis and unadjusted/adjusted (age at PARPi initiation, line number, practice type) hazard ratios (HR/aHR) from Cox proportional hazards models adjusted for survival bias. Results: Out of 829 mCRPC cases, BRCA1/2 alts were detected in 15 (1.8%) and 71 (8.6%) respectively, with 2 cases included in both groups. 26% of BRCAalts were BRCAdel, 67% were coding mutations, and 7% were genomic rearrangements. 25 (28%) BRCAalt pts were treated with PARPi, 11/25 in the 1st or 2nd line setting including 43% of BRCAdel and 44% of other BRCAalt cohorts. Median age at PARPi initiation was 70 yrs and 88% were treated in community practices. TTD was significantly longer in the BRCAdel (n = 7) cohort vs. other BRCAalt cohort (n = 18) (22.7 vs. 9.2 months; HR: 0.16 [0.03-0.74]; aHR: 0.13 [0.02 – 0.92]) while a statistically nonsignificant difference in median OS was observed (31.5 vs. 11.9 months; HR: 0.20 [0.02-1.58]; aHR: 0.24 [0.02-3.15]). In comparison, no statistically significant difference in TTD was observed for BRCAdel (n= 7) vs. other BRCAalts (n=19) pts treated with 1st line hormonal therapies (abiraterone or enzalutamide) (3.4 vs. 5.7 months; HR: 1.16 [0.45-2.98]; aHR: 0.72 [0.25-2.10]). Follow up analysis with more pts and somatic/germline status and zygosity of BRCAalts will be presented. Conclusions: These data suggest a differential benefit from PARPi therapy across BRCAalt subgroups. This observation may in part be explained by the inability to develop reversion mutations to restore BRCA function in tumors with BRCAdel. Further studies are warranted to fully assess the association of BRCAalt type with outcomes to PARPi-based treatments.

310 Background: Trastuzumab (T) plus chemotherapy is standard of care for pts with HER2+ adv GE cancer. Selection for T relies on HER2+ result by immunohistochemistry (IHC) +/- in-situ hybridization (ISH); ERBB2 amplification by comprehensive genomic profiling (CGP) also predicts benefit. As CGP use increases, it is important to explore associations of IHC/ISH and CGP result agreement with clinical outcomes in pts with adv GE cancer. Methods: Pts with adv GE cancer were selected from the Flatiron Health-Foundation Medicine (FMI) clinico-genomic database (CGDB), a nationwide de-identified EHR-derived clinical database linked to FMI genomic data. Pts treated from 01/2011-12/2018 with CGP data for tissue specimens collected before 1L were included. Agreement between HER2 status by IHC +/- ISH v ERBB2 amplification by CGP was assessed. For 1L containing T, time to tx discontinuation (TTD) and overall survival (OS) from 1L start stratified by HER2:ERBB2 agreement and ERBB2 copy number (CN) [ERBB2+ = CN >4] were estimated with unadjusted Kaplan-Meier analysis and adjusted (practice type, sex, age at adv dx) hazard ratios (aHR) from Cox proportional hazards models. Results: Of 596 HER2-tested pts with adv GE cancer in CGDB, 174 (29%) were HER2+ by IHC/ISH. Median age at adv dx was 63 y; 76.5% were male and 97% had adenocarcinoma. Overall HER2:ERBB2 agreement was 91%. Of 123 HER2+ 1L T-treated pts, median TTD and OS were longer for HER2+:ERBB2+ (concordant; n = 93) v HER2+:ERBB2- pts (discordant; n = 30): TTD, 5.2 v 0.8 months, aHR 0.46 (0.29-0.70); OS 14.8 v 7.5 months, aHR 0.38 (0.21-0.68). Median OS was 22.0 vs 8.4 months for 1L T-treated pts with ERBB2 CN > 30 (median) v CN ≤30 (aHR 0.69 [0.37-1.27]). Conclusions: In this large real-world clinico-genomic dataset, HER2:ERBB2 agreement was high in tested pts with adv GE cancer. 1L T-treated pts with discordant tests (HER2+:ERBB2-) had significantly shorter TTD and OS. Pts with higher ERBB2 CN had longer OS, but this finding was not significant after adjusting for covariates. Further research is needed to explore associations between HER2:ERBB2 agreement and clinical outcomes in this population.

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.

2630 Background: PD-L1 expression and TMB, as a proxy for neoantigen burden, have been correlated with response to IO in advanced NSCLC (aNSCLC) clinical trials, but their combined utility is unclear. We assessed TMB and PD-L1 as predictors of response in aNSCLC patients (pts) after IO monotherapy in a real-world setting. Methods: Pts had a diagnosis of aNSCLC, comprehensive genomic profiling of 186-315 genes/1.1 megabase (Mb), PD-L1 testing of pre-IO specimens, and were treated in the Flatiron Health network (1/2011 - 6/2018). Clinical characteristics and real-world tumor response (rwTR) were obtained via technology-enabled abstraction of clinician notes and radiology/pathology reports, and linked to genomic data in the Flatiron Health-Foundation Medicine Clinico-Genomic Database. A general additive model examined the predictive value of TMB (as continuous measure) and PD-L1 level on rwTR. A reduced PD-L1-only model was compared to the full model using Akaike Information Criterion (AIC). rwTR predictions at representative TMB and PD-L1 levels were calculated. Results: Of 426 pts, PD-L1 expression was high (≥50%) in 140, low (1-49%) in 123, and negative (

Introduction Strategic and budgetary considerations have shifted local health departments (LHDs) away from safety net clinical services and toward population-focused services. Federally Qualified Health Centers (FQHCs) play an increasing role in the safety net, and may complement or substitute for LHD clinical services. The authors examined the association between FQHC service levels in communities and the presence of specific LHD clinical services in 2010 and 2013. Methods Data from LHD surveys and FQHC service data were merged for 2010 and 2013. Multivariate regression and instrumental variable methods were used to examine FQHC service levels that might predict related LHD service presence or discontinuation from 2010 to 2013. Results There were modest reductions in LHD service presence and increases in FQHC service volume over the time period. LHD primary care and dental service presence were inversely associated with higher related FQHC service volume. LHD prenatal care service presence, as well as a measure of change in general service approach, were not significantly associated with FQHC service volume. Conclusions LHDs were less likely to provide certain clinical services where FQHCs provide a greater volume of services, suggesting a substitution effect. However, certain clinical services, such as prenatal care, may complement the public health mission—and LHDs may be strategically placed to continue to deliver these services.

LBA3579 Background: Few studies have directly compared health care utilization, costs, and outcomes between geographically similar patients (pts) treated in the U.S.’ multi-payer health system versus Canada’s single-payer system. Using cancer registry and claims data, we assessed systemic therapy (ST) use, cost, and survival for metastatic colorectal cancer (mCRC) pts in Western Washington (WW) and British Columbia (BC). Methods: Pts age ≥ 18 diagnosed with mCRC in 2010 and later were identified from 1) the BC Cancer Agency database and 2) a regional database linking WW SEER to claims from two large commercial insurers. Demographic and treatment characteristics for the two populations were compared using two-sample T tests. ST costs (first-line and lifetime) were expressed as mean per patient per month costs; Canadian costs were expressed in US dollars using the Purchasing Power Parity for Health in 2009. Median survival was reported for both populations. Results: 1622 BC pts and 575 WW pts were included in the analysis. BC pts were more likely to be older (median age 60 vs 66) and male (57% vs 48%, p = < 0.01). A greater proportion of WW versus BC pts received ST (79% vs. 68%, p < 0.01). FOLFIRI plus bevacizumab was the most common first-line regimen in BC (32%) while FOLFOX was the most common first-line regimen in WW (39%). The mean monthly cost of first-line therapy per patient was significantly higher in WW than BC ($12,345 vs $6,195, p = < 0.01), and this was true for all regimens assessed. Mean lifetime monthly ST costs were significantly higher in WW ($7,883 vs $4,830, p = < 0.01). There was no difference in median overall survival between populations among those receiving ST (21.4 months (95% CI 18.0-26.2) in WW and 22.1 months (20.5-23.7) in BC) or among those not receiving ST (5.4 months (2.4-7.7) WW versus 6.3 months (5.2-7.3) BC). Conclusions: Utilization and cost of ST for mCRC was significantly higher for patients in WW compared to BC without differences in overall survival in treated and untreated patients.

823 Background: Few studies have examined how patterns of care relate to clinical consensus guidelines for metastatic colorectal cancer (mCRC) in real-world settings. This study investigated treatment patterns around systemic therapies for older mCRC patients using SEER-Medicare data. Methods: We utilized data from a linkage of national Medicare claims data with records from the 12 Surveillance, Epidemiology, and End Results (SEER) regions for patients diagnosed with stage IV CRC between 2011 and 2014. Other inclusion criteria included adenocarcinoma histology, being > 65 years of age, and continuous Part A/B enrollment 12 months prior to diagnosis. We conducted bivariate analysis and multivariate modeling to evaluate the association between age, race, gender, SEER region, and comorbidity score with receipt of systemic therapy. We examined first and subsequent lines of therapy, and classified them as adherent or non-adherent to NCCN guidelines. Results: Of 102,461 CRC patients, 6,360 (6.2%) patients had evidence of metastatic disease and met all inclusion criteria. 3,155 (49.6%) received no systemic therapy. Of the 2,976 (46.8%) who received systemic therapy with identifiable regimens, FOLFOX/CAPOX was the most common 1L regimen (32.9%), followed by 5-FU or capecitabine alone (26.4%) – both identified as guideline-adherent therapies. Non-guideline adherent regimens (such as use of single-agent oxaliplatin or bevacizumab) were uncommon as 1L therapies (1.4%). 1,553 patients (52.2%) progressed to a 2L therapy, 715 (24.0%) progressed to a 3L therapy, and 320 (10.8%) to a 4L therapy. A large proportion of 2L (26.9%) and 3L (24.2%) treatments contained bevacizumab. 96 patients (3.2%) received regorafenib, representing 6.7% of 3L and 10.6% of 4L therapies. Patients who did not receive systemic therapy were older (mean age of 80.8 vs 74.9) and had multiple comorbidities (63.1% vs 48.4% with Klabunde score > 1). Conclusions: In a Medicare-insured mCRC cohort, patients generally received systemic therapy adhering to consensus guidelines. However, many patients did not receive systemic therapy – suggesting there may be delays in diagnosis and barriers to treatment which lower systemic therapy utilization.

Background Adolescent substance use rates in rural areas of the United States, such as upstate New York, have risen substantially in recent years, calling for new intervention approaches in response to this trend. The Mentor Foundation USA conducts the Living the Example (LTE) campaign to engage youth in prevention using an experiential approach. As part of LTE, youth create their own prevention messages following a training curriculum in techniques for effective messaging and then share them via social media. This paper reports on a pilot evaluation of the LTE program. Objective To conduct a pilot test of LTE in two rural high schools in upstate New York. We hypothesized that positive antidrug brand representations could be promoted using social media strategies to complement the Shattering the Myths (STM) in-person, event-based approach (hypothesis 1, H1), and that youth would respond positively and engage with prevention messages disseminated by their peers. We also hypothesized that exposure to the social media prevention messages would be associated with more positive substance use avoidance attitudes and beliefs, reductions in future use intentions, and decreased substance use at posttest (hypothesis 2, H2). Methods We adapted a previously published curriculum created by the authors that focuses on branding, messaging, and social media for prevention. The curriculum consisted of five, one-hour sessions. It was delivered to participating youth in five sequential weeks after school at the two high schools in late October and early November 2016. We designed a pre- and posttest pilot implementation study to evaluate the effects of LTE on student uptake of the intervention and short-term substance use and related outcomes. Working at two high schools in upstate New York, we conducted a pilot feasibility evaluation of LTE with 9th-grade students (ie, freshmen) at these high schools. We administered a 125-item questionnaire online to capture data on media use; attitudes toward social media; next 30-day personal drug use intentions; personal reasons to use drugs; reasons participants believe their peers would use drugs; self-reported exposure to the LTE program; and receptivity to the LTE program, among those reporting exposure. We constructed multivariable logistic regression models to analyze the relationship between program receptivity and outcomes. First, in a cross-sectional logistic regression model, we regressed self-reported LTE message receipt on drug use intent and actions related to LTE messaging. Then, for analysis of participants with matched pre- and posttest responses, we used multilevel generalized estimating equation (GEE) techniques to model changes in behavior from baseline to follow-up. Results Youth reported increased intentions to use marijuana (odds ratio [OR] 2.134, P=.02) between pre- and posttest. However, youth who reported exposure and receptivity to LTE reported a significant decrease in intentions (OR 0.239, P=.008). We observed a similar pattern for sedatives/sleeping pills—an increase in intentions overall (OR 1.886, P=.07), but a decrease among youth who reported exposure and receptivity to LTE (OR 0.210, P=.02). We saw the same pattern for use of any drug—an increase in reported intentions overall (OR 2.141, P=.02), but a decrease among youth who reported exposure and receptivity to LTE (OR 0.111, P=.004). Conclusions We observed some evidence of significant LTE program effects. Social media may be an effective strategy for peer-to-peer substance use prevention in the future. These findings point both to the potential of LTE and the social media diffusion model and to the need for more research on a larger scale with an expanded youth population in the future.

e15011 Background: Few studies have examined patterns of care relating to guideline-recommended therapies for metastatic colorectal cancer (mCRC) in real-world settings. The goal of this study was to investigate treatment patterns for initial and subsequent therapies for mCRC patients in two large commercial plans in Washington State, USA. Methods: We utilized the Hutchinson Institute for Cancer Outcomes Research linkage of Western Washington Cancer Surveillance System (CSS) SEER data with claims from Regence BlueShield and Premera BlueCross (representing 20% of the WA insured population) for patients diagnosed with mCRC between 2012 and 2016. We identified all patients with Stage IV CRC at diagnosis or stage I-III CRC with subsequent claims suggesting metastatic recurrence. We conducted descriptive analysis and multivariate modeling to evaluate the association between age, race, gender, and rurality with receipt of systemic therapy. We examined 1L (first line) regimens received in the first 15 days of treatment, and classified them as adherent or not to NCCN guidelines. In light of recent FDA approval for regorafenib (9/2012) and TAS-102 (9/2015), we examined use of these therapies for refractory mCRC. Results: Among 4,536 CRC cases identified in the database, 426 patients had evidence of metastatic disease and met all inclusion criteria. 87 (20.4%) received no systemic therapy. Of the 339 (79.5%) who received systemic therapy, FOLFOX was the most common 1L regimen (29.5%), followed by FOLFOX+bevacizumab (12.3%). There was evidence of 1L treatment outside of NCCN guidelines – 8.5% of patients received single-agent bevacizumab, and 8.0% received single-agent oxaliplatin. Patients who did not receive systemic therapy were more likely to be older and live in a large metropolitan area. For subsequent therapies, 24 (7.1%) patients received regorafenib, and 5 (1.5%) received TAS-102. Conclusions: In a commercially-insured mCRC cohort, a majority received 1L guideline-based therapy. Many patients did not receive systemic therapy despite current recommendations - further evaluation of factors contributing to these decisions are warranted. Use of regorafenib and TAS-102 was uncommon.

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.

BackgroundThe 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. ObjectiveIn this study, investigators aimed to evaluate Text4baby in the military women’s population. MethodsInvestigators 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. ResultsFor 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. ConclusionsText4baby 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.

The Dominantly Inherited Alzheimer's Network Trials Unit (DIAN-TU) was formed to direct the design and management of interventional therapeutic trials of international DIAN and autosomal dominant Alzheimer's disease (ADAD) participants. The goal of the DIAN-TU is to implement safe trials that have the highest likelihood of success while advancing scientific understanding of these diseases and clinical effects of proposed therapies. The DIAN-TU has launched a trial design that leverages the existing infrastructure of the ongoing DIAN observational study, takes advantage of a variety of drug targets, incorporates the latest results of biomarker and cognitive data collected during the observational study, and implements biomarkers measuring Alzheimer's disease (AD) biological processes to improve the efficiency of trial design. The DIAN-TU trial design is unique due to the sophisticated design of multiple drugs, multiple pharmaceutical partners, academics servings as sponsor, geographic distribution of a rare population and intensive safety and biomarker assessments. The implementation of the operational aspects such as home health research delivery, safety magnetic resonance imagings (MRIs) at remote locations, monitoring clinical and cognitive measures, and regulatory management involving multiple pharmaceutical sponsors of the complex DIAN-TU trial are described.

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.

ObjectiveThe 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.DesignSecondary analysis of baseline data from a social marketing intervention designed to change household dietary practices among parents of 3- to 7-year-old children.SettingA community sample drawn from six low-income, primarily minority neighbourhoods in Chicago, IL, USA.SubjectsFrom 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.ResultsLogistic 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.ConclusionsOur 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.

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.

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.

Objectives To determine effects of the 5-4-3-2-1 Go! community social marketing campaign on obesity risk factors. Methods We randomly assigned 524 parents of 3- to 7-year-old children to receive 5-4-3-2-1 Go! counseling or not. We surveyed parents about 5-4-3-2-1 Go! behaviors and perceptions of children's behaviors at baseline and one year later. We conducted multivariable logistic regression for each outcome. Results Parents who received counseling consumed more fruits and vegetables at follow-up (OR 1.749, [95% CI: 1.01-3.059]). Parental exposure to messaging at children's school events was associated with higher water consumption (6.879, [1.954-24.212]). Conclusions 5-4-3-2-1 Go! is a promising intervention.