Engaging with Rural Communities for Colorectal Cancer Screening Outreach Using Modified Boot Camp Translation.

BACKGROUND: Colorectal cancer (CRC) incidence and mortality are disproportionately high among rural residents and Medicaid enrollees. OBJECTIVES: To address disparities, we used a modified community engagement approach, Boot Camp Translation (BCT). Research partners, an advisory board, and the rural community informed messaging about CRC outreach and a mailed fecal immunochemical test program. METHODS: Eligible rural patients (English-speaking and ages 50-74) and clinic staff involved in patient outreach participated in a BCT conducted virtually over two months. We applied qualitative analysis to BCT transcripts and field notes. RESULTS: Key themes included: the importance of directly communicating about the seriousness of cancer, leveraging close clinic-patient relationships, and communicating the test safety, ease, and low cost. CONCLUSIONS: Using a modified version of BCT delivered in a virtual format, we were able to successfully capture community input to adapt a CRC outreach program for use in rural settings. Program materials will be tested during a pragmatic trial to address rural CRC screening disparities.

Methods for scaling up an outreach intervention to increase colorectal cancer screening rates in rural areas.

BACKGROUND: Mailed fecal immunochemical test (FIT) outreach and patient navigation are evidence-based practices shown to improve rates of colorectal cancer (CRC) and follow-up in various settings, yet these programs have not been broadly adopted by health systems and organizations that serve diverse populations. Reasons for low adoption rates are multifactorial, and little research explores approaches for scaling up a complex, multi-level CRC screening outreach intervention to advance equity in rural settings. METHODS: SMARTER CRC, a National Cancer Institute Cancer Moonshot project, is a cluster-randomized controlled trial of a mailed FIT and patient navigation program involving 3 Medicaid health plans and 28 rural primary care practices in Oregon and Idaho followed by a national scale-up trial. The SMARTER CRC intervention combines mailed FIT outreach supported by clinics, health plans, and vendors and patient navigation for colonoscopy following an abnormal FIT result. We applied the framework from Perez and colleagues to identify the intervention's components (including functions and forms) and scale-up dissemination strategies and worked with a national advisory board to support scale-up to additional organizations. The team is recruiting health plans, primary care clinics, and regional and national organizations in the USA that serve a rural population. To teach organizations about the intervention, activities include Extension for Community Healthcare Outcomes (ECHO) tele-mentoring learning collaboratives, a facilitation guide and other materials, a patient navigation workshop, webinars, and individualized technical assistance. Our primary outcome is program adoption (by component), measured 6 months after participation in an ECHO learning collaborative. We also assess engagement and adaptations (implemented and desired) to learn how the multicomponent intervention might be modified to best support broad scale-up. DISCUSSION: Findings may inform approaches for adapting and scaling evidence-based approaches to promote CRC screening participation in underserved populations and settings. TRIAL REGISTRATION: Registered at ClinicalTrials.gov (NCT04890054) and at the NCI's Clinical Trials Reporting Program (CTRP no.: NCI-2021-01032) on May 11, 2021.

A 73-gene proliferative transcriptomic signature predicts uterine serous carcinoma patient survival and response to primary therapy.

OBJECTIVES: To develop a transcriptomic signature capable of predicting overall survival (OS) for uterine serous carcinoma (USC). METHODS: RNAseq data for 58 USC patients were obtained from TCGA. Expression of 73 candidate genes was measured for 67 Augusta University (AU) samples using NanoString technology. RESULTS: Analysis of the TCGA RNAseq data identified 73 genes that individually predict prognosis for USC patients and an elastic net model with all 73 genes (USC73) distinguishes a good OS group with low USC73 score from a poor OS group with high USC73 score (5-year OS = 83.3% and 13.3% respectively, HR = 40.1; p = 3 × 10-8). This finding was validated in the independent AU cohort (HR = 4.3; p = 0.0004). The poor prognosis group with high USC73 score consists of 37.9% and 32.8% of patients in the TCGA and AU cohort respectively. USC73 score and pathologic stage independently contribute to OS and together provide the best prognostic value. Early stage, low USC73 patients have the best prognosis (5-year OS = 85.1% in the combined dataset), while advanced stage, high USC73 patients have the worst prognosis (5-year OS = 6.4%, HR = 30.5, p = 1.2 × 10-12). Consistent with the observed poor survival, primary cell cultures from high USC73 patients had higher proliferation rate and cell cycle progression; and high USC73 patients had lower rates of complete response to standard therapy. CONCLUSIONS: The USC73 transcriptomic signature and stage independently predict OS of USC patients and the best prediction is achieved using USC73 and stage. USC73 may also serve as a therapeutic biomarker to guide patient care.

Fertility counseling before cancer treatment and subsequent reproductive concerns among female adolescent and young adult cancer survivors.

BACKGROUND: Fertility counseling before cancer treatment has been advocated by clinical guidelines, though little is known about its long-term impact on the unique reproductive concerns of female adolescent and young adult (AYA) cancer survivors. The goal of this study was to measure the association between fertility counseling by fertility specialists before cancer treatment and subsequent reproductive concerns. METHOD: A cross-sectional analysis was performed among 747 AYA survivors aged 18-40 years who had been recruited from cancer registries and physician and advocacy group referrals between 2015 and 2017. Participants self-reported information on past fertility counseling at cancer diagnosis, cancer type and treatment, and current reproductive concerns, as measured using the multidimensional Reproductive Concerns After Cancer scale. Multivariable log-binomial regression models tested associations between fertility counseling and reproductive concerns. RESULTS: The mean age of the cohort was 33.0 years (standard deviation, 5.1 years), and the mean period since diagnosis was 7.7 years (standard deviation, 5.0 years). Seventy-three percent of participants were white, and 24% were Hispanic. Fertility counseling was reported by 19% of survivors; moderate to high overall reproductive concerns were reported by 44% of participants. In adjusted analysis, fertility counseling was significantly associated with moderate to high reproductive concerns (risk ratio, 1.22; 95% confidence interval, 1.02-1.45) and not modified by exposure to fertility-threatening treatments (Pinteraction = .23). CONCLUSION: A large proportion of AYA cancer survivors across cancer types and treatment exposures reported moderate to high reproductive concerns, suggesting that there is a need to address these cancer-specific reproductive health concerns after treatment. Higher concerns, even with counseling, suggests the need to improve the quality of fertility counseling throughout the cancer continuum.

Design of a randomized controlled trial on the efficacy of a reproductive health survivorship care plan in young breast cancer survivors.

BACKGROUND: Young breast cancer survivors (YBCS) have unmet needs for managing hot flashes, fertility-related concerns, sexual health, and contraception. PURPOSE: Describe the design and participant characteristics of a randomized controlled trial testing the efficacy of the survivorship care plan on reproductive health (SCP-R) intervention on improving hot flashes, fertility-related concerns, sexual health, and contraception in YBCS. METHODS: SCP-R is a web-based intervention with text message support encompassing evidence- based practices on four reproductive health issues. YBCS with ≥1 reproductive health issue are randomized to intervention (full SCP-R access) or attention control (access to list of online resources) arms with 24-week follow-up. The primary outcome will be improvement of at least one reproductive health issue measured by validated self-report instruments. Each YBCS nominated one healthcare provider (HCP), who can access the same materials as their patient. HCP outcomes are preparedness and confidence in discussing each issue. RESULTS: Among 318 YBCS screened, 57.2% underwent randomization. Mean age was 40.0 (SD 5.9), and mean age at cancer diagnosis was 35.6 (SD 5.4). Significant hot flashes, fertility-related concerns, vaginal symptoms, and inadequate contraception were reported by 50.5%, 50%, 46.7%, 62.1% of YBCS, respectively; 70.9% had multiple issues. Among 165 nominated HCPs, 32.7% enrolled. The majority of HCPs reported preparedness (68.5-90.7%) and confidence (50.0-74.1%) in discussing reproductive health issues with YBCS. HCPs were least likely to report preparedness or confidence in discussing fertility-related concerns. CONCLUSION: Conducting a trial for improving YBCS reproductive health online is feasible, providing a mechanism to disseminate evidence-based management.

Randomized controlled trial of increasing physical activity on objectively measured and self-reported cognitive functioning among breast cancer survivors: The memory & motion study.

BACKGROUND: Increasing physical activity can improve cognition in healthy and cognitively impaired adults; however, the benefits for cancer survivors are unknown. The current study examined a 12-week physical activity intervention, compared with a control condition, on objective and self-reported cognition among breast cancer survivors. METHODS: Sedentary breast cancer survivors were randomized to an exercise arm (n = 43) or a control arm (n = 44). At baseline and at 12 weeks, objective cognition was measured with the National Institutes of Health Cognitive Toolbox, and self-reported cognition using the Patient-Reported Outcomes Measurement Information System scales. Linear mixed-effects regression models tested intervention effects for changes in cognition scores. RESULTS: On average, participants (n = 87) were aged 57 years (standard deviation, 10.4 years) and were 2.5 years (standard deviation, 1.3 years) post surgery. Scores on the Oral Symbol Digit subscale (a measure of processing speed) evidenced differential improvement in the exercise arm versus the control arm (b = 2.01; P < .05). The between-group differences in improvement on self-reported cognition were not statistically significant but were suggestive of potential group differences. Time since surgery moderated the correlation, and participants who were ≤2 years post surgery had a significantly greater improvement in Oral Symbol Digit score (exercise vs control (b = 4.00; P < .01), but no significant improvement was observed in patients who were >2 years postsurgery (b = -1.19; P = .40). A significant dose response was observed with greater increased physical activity associated with objective and self-reported cognition in the exercise arm. CONCLUSIONS: The exercise intervention significantly improved processing speed, but only among those who had been diagnosed with breast cancer within the past 2 years. Slowed processing speed can have substantial implications for independent functioning, supporting the potential importance of early implementation of an exercise intervention among patients with breast cancer. Cancer 2018;124:192-202. © 2017 American Cancer Society.

Lupus Skin Is Primed for IL-6 Inflammatory Responses through a Keratinocyte-Mediated Autocrine Type I Interferon Loop.

Cutaneous lupus erythematosus is a disfiguring and common manifestation in systemic lupus erythematosus, and the etiology of this predisposition for cutaneous inflammation is unknown. Here, we sought to examine the keratinocyte as an important source of IL-6 and define the mechanism for its increased production in cutaneous lupus erythematosus. Evaluation of discoid and subacute cutaneous lupus erythematosus lesions showed significant epidermal up-regulation of IL-6 compared with control via real-time PCR and immunohistochemistry. Keratinocytes from unaffected skin of lupus patients produced significantly more IL-6 compared with healthy control subjects after exposure to toll-like receptor 2, 3, or 4 agonists or exposure to UVB radiation. Pretreatment with type I interferons (IFN-α and IFN-κ) increased IL-6 production by control keratinocytes, and type I IFN blockade decreased IL-6 secretion by lupus keratinocytes. Secretion of keratinocyte-specific IFN-κ was significantly increased after toll-like receptor 2 and UVB treatment in lupus keratinocytes, and neutralization of IFN-κ decreased IL-6 production by lupus keratinocytes. Thus, lupus keratinocytes are primed for IL-6 hyperproduction in a type I IFN-dependent manner. Increased production of IFN-κ by lupus keratinocytes drives this response, indicating that IFN-κ may play a pathogenic role in cutaneous lupus erythematosus and serve as a target for treatment.

Changes in the Healthy Beverage Index in Response to an Intervention Targeting a Reduction in Sugar-Sweetened Beverage Consumption as Compared to an Intervention Targeting Improvements in Physical Activity: Results from the Talking Health Trial.

The recently developed Healthy Beverage Index (HBI) was designed to evaluate overall beverage intake quality (including total fluid consumption and beverage calories), yet no known intervention studies have assessed longitudinal changes to the HBI. The objective of this investigation was to assess changes in HBI scores in response to a sugar-sweetened beverage (SSB) reduction trial as compared to a physical activity comparison group. Participants were enrolled into a six-month, community-based, controlled behavioral trial and randomized into either a SSB reduction group (SIPsmartER) or a physical activity group (MoveMore). Correlations and multilevel mixed-effects linear regression with intention-to-treat analyses are presented. Total HBI score significantly increased for SIPsmartER (n = 149) (mean increase = 7.5 points (5.4, 9.7), p ≤ 0.001) and MoveMore (n = 143) (mean increase = 3.4 points (1.6, 5.2), p ≤ 0.001) participants, with a significant between group effect (p ≤ 0.05), over the six-month intervention. Other significant changes in HBI components for SIPsmartER included increased SSB and total beverage calorie scores, and decreased low-fat milk and diet soda scores. Changes in total HBI scores were significantly correlated with changes in total Healthy Eating Index-2010 scores (r = 0.15, p ≤ 0.01). Our findings suggest that individual HBI component scores, beyond the SSB component, are influenced by intervention strategies that primarily focus on SSB reduction.

Evaluating the ovarian cancer gonadotropin hypothesis: a candidate gene study.

OBJECTIVE: Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. METHODS: Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations. RESULTS: We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p=0.045, mucinous), LHCGR (p=0.046, high-grade serous), GNRH (p=0.041, high-grade serous), and FSHB (p=0.036, overall invasive). There was also suggestive evidence for INHA (p=0.060, overall invasive). CONCLUSIONS: Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available.