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Abstract Background Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N +) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N + vs N0) and distance from anal verge (0–4; 4–8; 8–12 cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3–4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8–12 (± 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha = 0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion Building on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial registration Clinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Background: Fear of cancer recurrence (FCR), cancer-distress, depression, and anxiety are prevalent concerns among women with gynecologic and other understudied cancers, especially among women of color and lower socioeconomic status (SES). Evidence indicates that mind-body interventions are effective in reducing such distress. This study evaluates (1) proof-of-concept of an integrated group yoga and psychological intervention in alleviating distress among women with gynecologic, gastrointestinal, and thoracic cancers and (2) differences in efficacy across social and economic factors. Methods: One hundred twenty-five participants were enrolled in a 10-week, single-arm, integrated group intervention utilizing mindfulness meditation, psychotherapy skills, and yoga. They completed measures of FCR, cancer-distress, depression, and anxiety at baseline and following intervention. Mixed-linear models evaluated change in outcomes across the intervention and moderating effects of age, minority status, and SES among 51 participants with available data. Results: Reductions in total ( b = −2.06, P = .012) and somatic depressive symptoms ( b = −1.79, P = .002) and state anxiety ( b = −6.21, P = .005) were observed across the sample. Higher SES was associated with greater reductions in psychosocial distress related to FCR ( b = −0.74, P = .050), and in total (b = −1.06, P = .049) and affective depressive symptoms ( b = −0.76, P = .006). Women of color experienced greater declines in somatic symptoms compared to non-Hispanic White women ( b = −2.71, P = .031), with women of color experiencing lower SES exhibiting greatest reduction in these symptoms ( b = 1.73, P = .026). Conclusions: This study demonstrates proof-of-concept that an integrated psychological and yoga intervention may reduce depressive symptoms and state anxiety among women with gynecologic, gastrointestinal, and thoracic cancers, with racial and/or ethnic minority status and SES moderating some of these effects. Future research should examine intervention feasibility and acceptability among diverse women with cancer and evaluate efficacy using a randomized controlled trial design. Trial registration: ClinicalTrials.gov NCT03385577

Abstract The University of Florida Health conducted a pragmatic implementation of a pharmacogenetics (PGx) panel‐based test to guide medications used for supportive care prescribed to patients undergoing chemotherapy. The implementation was in the context of a pragmatic clinical trial for patients with non‐hematologic cancers being treated with chemotherapy. Patients were randomized to either the intervention arm or control arm and received PGx testing immediately or at the end of the study, respectively. Patients completed the MD Anderson Symptom Inventory (MDASI) to assess quality of life (QoL). A total of 150 patients received PGx testing and enrolled in the study. Clinical decision support and implementation infrastructure were developed. While the study was originally planned for 500 patients, we were underpowered in our sample of 150 patients to test differences in the patient‐reported MDASI scores. We did observed a high completion rate (92%) of the questionnaires; however, there were few medication changes (n = 6 in the intervention arm) based on PGx test results. Despite this, we learned several lessons through this pragmatic implementation of a PGx panel‐based test in an outpatient oncology setting. Most notably, patients were less willing to undergo PGx testing if the cost of the test exceeded $100. In addition, to enhance PGx implementation success, reoccurring provider education is necessary, clinical decision support needs to appear in a more conducive way to fit in with oncologists' workflow, and PGx test results need to be available earlier in treatment planning.

Abstract Background For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. Methods The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16–26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. Discussion The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. Trial registration ClinicalTrials.gov: NCT05673148, registered December 21, 2022.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss. Methods Treatment naïve patients with PDAC who underwent pancreatectomy at a single institution between 2012 and 2020 were identified retrospectively. Patients with pancreatic head or distal tumours were matched by sex, age, N and T stage. Serologic and anthropometric variables were obtained at the time of diagnosis. Skeletal muscle index (SMI), muscle radiation attenuation (MRA) and adiposity were measured. The primary outcome was presence of significant weight loss [>5% body weight (BW) loss in past 6 months]. Signed rank tests, Cochran Mantel Haenszel tests and Kaplan–Meier survival analysis are presented. RNA‐seq of tumours was performed to explore enriched pathways related to cachexia and weight loss. Results Pancreatic head tumours (n = 24) were associated with higher prevalence (70.8% vs. 41.7%, P = 0.081) and degree of weight loss (7.9% vs. 2.5%, P = 0.014) compared to distal tumours (n = 24). BMI (P = 0.642), SMI (P = 0.738) and MRA (P = 0.478) were similar between groups. Combining BW loss, SMI and MRA into a composite score, patients with pancreatic head cancers met more criteria associated with poor prognosis (P = 0.142). Serum albumin (3.9 vs. 4.4 g/dL, P = 0.002) was lower and bilirubin (4.5 vs. 0.4 mg/dL, P

Abstract Background Undiagnosed Type 2 diabetes (T2D) has been associated with advanced stage cancer at diagnosis, higher mortality, and lower long‐term all‐cause survival. This was a RCT pilot study to examine the feasibility of a nurse‐led T2D intervention for adults with newly diagnosed cancer (≤3 months), and T2D, undiagnosed or untreated with medication, conducted at an outpatient oncology clinic affiliated with a large academic institution. Methods Participants needed to meet the eligibility criteria including a HbA1c level between 6.5% and 9.9%. Randomization was 1:1 to a 3‐month intervention that consisted of nursing‐led diabetes education and immediate initiation of metformin versus referral to primary care for usual care (control). Results Three hundred and seventy nine patients were screened using EHR, 55 agreed to participate, and 3 had eligible HbA1c levels and were randomized in the study. Primary reasons for study exclusion included life expectancy ≤2 years (16.9%), current use or inability to tolerate metformin (14.8%), and abnormal labs that contraindicated metformin use (13.9%). Conclusion This study was not feasible due to recruitment inefficiencies, but acceptable to all who qualified.

Abstract Background Prior studies on the association between asthma and cancer show inconsistent results. This study aimed to generate additional evidence on the association between asthma and cancer, both overall, and by cancer type, in the United States. Method We conducted a retrospective cohort study using 2012–2020 electronic health records and claims data in the OneFlorida+ clinical research network. Our study population included a cohort of adult patients with asthma (n = 90,021) and a matching cohort of adult patients without asthma (n = 270,063). We built Cox proportional hazards models to examine the association between asthma diagnosis and subsequent cancer risk. Results Our results showed that asthma patients were more likely to develop cancer compared to patients without asthma in multivariable analysis (hazard ratio [HR] = 1.36, 99% confidence interval [CI] = 1.29–1.44). Elevated cancer risk was observed in asthma patients without (HR = 1.60; 99% CI: 1.50–1.71) or with (HR = 1.11; 99% CI: 1.03–1.21) inhaled steroid use. However, in analyses of specific cancer types, cancer risk was elevated for nine of 13 cancers in asthma patients without inhaled steroid use but only for two of 13 cancers in asthma patients with inhaled steroid use, suggesting a protective effect of inhaled steroid use on cancer. Conclusion This is the first study to report a positive association between asthma and overall cancer risk in the US population. More in‐depth studies using real‐word data are needed to further explore the causal mechanisms of asthma on cancer risk.

Abstract Background Patient and clinician reminders were implemented as part of an adherence improvement project at University of Florida (UF) Internal Medicine Clinics. We sought to assess colorectal cancer (CRC) screening completion rates among patients not up-to-date with screening following distribution of reminders and to identify characteristics correlated with screening outcomes. Methods Retrospective chart review was performed for patients not up-to-date with CRC screening for whom at least one reminder (patient and/or clinician) was issued in June 2018. The primary endpoint, the completion of a CRC screening test, is characterized as the ratio of completed screening tests to the number of patients not up-to-date with screening. All analyses were performed using R 4.0 software. Results Of the 926 patients included, 403 (44%; 95% CI, 0.40–0.47) completed a CRC screening test within 24 months following a reminder. Family history of CRC (relative risk (RR) 1.33; P = 0.007), flu immunization within two years of the reminder (RR 1.23; P = 0.019), and receiving a patient reminder either alone (RR 1.62; P

Abstract Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest of all common malignancies. Treatment is difficult and often complicated by the presence of cachexia. The clinical portrait of cachexia contributes to the poor prognosis experienced by PDAC patients and worsens therapeutic outcomes. We propose that low bone mineral density is a component of cachexia, which we explore herein through a retrospective review of all patients at our facility that underwent surgery for PDAC between 2011 and 2018 and compared to sex‐, age‐ and comorbidity‐matched control individuals. Data were abstracted from the medical record and pre‐operative computed tomography scans. Muscle mass and quality were measured at the L3 level and bone mineral density was measured as the radiation attenuation of the lumbar vertebral bodies. Patients with PDAC displayed typical signs of cachexia such as weight loss and radiologically appreciable deterioration of skeletal muscle. Critically, PDAC patients had significantly lower bone mineral density than controls, with 61.2% of PDAC patients categorized as osteopenic compared to 36.8% of controls. PDAC patients classified as osteopenic had significantly reduced survival (1.01 years) compared to patients without osteopenia (2.77 years). The presence of osteopenia was the strongest clinical predictor of 1‐ and 2‐year disease‐specific mortality, increasing the risk of death by 107% and 80%, respectively. Osteopenia serves as a test of 2‐year mortality with sensitivity of 76% and specificity of 58%. These data therefore identify impaired bone mineral density as a key component of cachexia and predictor of postoperative survival in patients with PDAC. The mechanisms that lead to bone wasting in tumor‐bearing hosts deserve further study.

Rural adults experience disparities in colorectal cancer screening, a trend even more distinct among rural Black adults. Healthcare disruptions caused by COVID-19 exacerbated inequities, heightening attention on virtual communication strategies to increase screening. Yet little is known about how rural adults perceive virtual human clinicians (VHCs). Given that identifying as rural influences perceived source credibility often through appearance judgments, the goal of this pilot was to explore how to develop VHCs that individuals highly identified with rurality find attractive. Between November 2018 and April 2019, we tested a culturally tailored, VHC-led telehealth intervention delivering evidence-based colorectal cancer prevention education with White and Black adults (N = 2079) in the United States recruited through an online panel who were non-adherent to screening guidelines and between 50 and 73 years of age. Participants were randomized on three factors (VHC race-matching, VHC gender-matching, Intervention type). Ordinal logistic regression models examined VHC appearance ratings. Participants with a high rural identity (AOR = 1.12, CI = [1.02, 1.23], p =.02) rated the VHCs more attractive. High rural belonging influenced VHC attractiveness for Black participants (AOR = 1.22, CI = [1.03, 1.44], p =.02). Also, Black participants interacting with a Black VHC and reporting high rural self-concept rated the VHC as more attractive (AOR = 2.22, CI = [1.27, 3.91], p =.01). Findings suggest adults for whom rural identity is important have more positive impressions of VHC attractiveness. For patients with strong rural identities, enhancing VHC appearance is critical to tailoring colorectal cancer prevention interventions.

The increased utilization of telehealth has provided patients with the opportunity to interact with racially diverse healthcare providers (HCPs). While evidence of racial stereotypes in healthcare is well documented, less is known about whether linguistic cues increase or decrease racial bias in healthcare interactions. The purpose of this pilot study was to use virtual clinicians (VCs) to examine how varying linguistic features affect patient perceptions of Black-identifying HCPs. Participants (N = 282) were recruited to participate in an online pilot study using a two-arm posttest-only experimental design. Participants were randomly assigned to interact with a Black VC that used vocal cues associated with either Standard American English (SAE) or African American English (AAE) on the topic of colorectal cancer. After the interaction, participants completed a posttest questionnaire. Resulting data were analyzed using mediation.

Liquid biopsy has progressed to its current use to diagnose and monitor cancer. Despite the recent advances in investigating cancer detection and diagnosis strategies, there is still a room for improvements in capturing CTCs. We developed an efficient CTC detection system by integrating gold nanoparticles with a microfluidic platform, which can achieve CTC capture within 120 min. Here, we report our development of a simple and effective way to isolate CTCs using antibodies attached on gold nanoparticles to the surface of a lateral filter array (LFA) microdevice. Our method was optimized using three pancreatic tumor cell lines, enabling the capture with high efficiency (90% ± 3.2%). The platform was further demonstrated for isolating CTCs from patients with metastatic pancreatic cancer. Our method and platform enables the production of functionalized, patterned surfaces that interact with tumor cells, enhancing the selective capture of CTCs for biological assays.

Abstract Background Understanding how older, minoritized patients attend to cues when interacting with web-based health messages may provide opportunities to improve engagement with novel health technologies. We assess acceptance-promoting and acceptance-inhibiting cues of a web-based, intervention promoting colorectal cancer (CRC) screening with a home stool test among Black women. Materials and methods Focus group and individual interview data informed iterative changes to a race- and gender-concordant virtual health assistant (VHA). A user-centered design approach was used across 3 iterations to identify changes needed to activate cues described as important; such as portraying authority and expertise. Questionnaire data were analyzed using non-parametric tests for perceptions of cues. Analysis was guided by the Technology Acceptance Model. Results Perceptions of interactivity, social presence, expertise, and trust were important cues in a VHA-delivered intervention promoting CRC screening. Features of the web-based platform related to ease of navigation and use were also discussed. Participant comments varied across the 3 iterations and indicated acceptance of or a desire to improve source cues for subsequent iterations. We highlight the specific key changes made at each of three iterative versions of the interactive intervention in conjunction with user perception of changes. Discussion Virtual agents can be adapted to better meet patient expectations such as being a trustworthy and expert source. Across three evolving versions of a Black, VHA, cues for social presence were particularly important. Social presence cues helped patients engage with CRC screening messages delivered in this novel digital context. Conclusions When using a VHA to disseminate health information, cues associated with acceptability can be leveraged and adapted as needed for diverse audiences. Patient characteristics (age, identity, health status) are important to note as they may affect perceptions of a novel health technologies ease of use and relevancy according to the leading models.

Abstract Background Undergoing cancer screening is a debatable topic in patients with cognitive impairment. In this study, we aimed to examine the utilization and predictors of breast and colorectal cancer screening among screening eligible, cognitively impaired individuals. Methods We analyzed the 2018 and 2019 National Health Interview Survey data (n = 12,965 and 24,782, respectively) on individuals eligible for breast or colorectal cancer screening. We calculated the percentage of cancer screening eligible individuals who received mammogram or colonoscopy by cognitive impairment status. We used multivariable logistic regression to examine whether having a recent mammogram or colonoscopy differed by cognitive impairment status, adjusting for covariates. Results We observed a significantly lower percentage of mammogram use in the screening eligible, cognitively impaired (mild or severe) versus unimpaired women. Adjusting for the covariates, the cognitively impaired women, mild (odds ratio [OR] = 0.85; p = 0.015) or severe (OR = 0.54; p

Abstract In this study, we explored the feasibility of using real-world data (RWD) from a large clinical research network to simulate real-world clinical trials of Alzheimer’s disease (AD). The target trial (i.e., NCT00478205) is a Phase III double-blind, parallel-group trial that compared the 23 mg donepezil sustained release with the 10 mg donepezil immediate release formulation in patients with moderate to severe AD. We followed the target trial’s study protocol to identify the study population, treatment regimen assignments and outcome assessments, and to set up a number of different simulation scenarios and parameters. We considered two main scenarios: (1) a one-arm simulation: simulating a standard-of-care (SOC) arm that can serve as an external control arm; and (2) a two-arm simulation: simulating both intervention and control arms with proper patient matching algorithms for comparative effectiveness analysis. In the two-arm simulation scenario, we used propensity score matching controlling for baseline characteristics to simulate the randomization process. In the two-arm simulation, higher serious adverse event (SAE) rates were observed in the simulated trials than the rates reported in original trial, and a higher SAE rate was observed in the 23 mg arm than in the 10 mg SOC arm. In the one-arm simulation scenario, similar estimates of SAE rates were observed when proportional sampling was used to control demographic variables. In conclusion, trial simulation using RWD is feasible in this example of AD trial in terms of safety evaluation. Trial simulation using RWD could be a valuable tool for post-market comparative effectiveness studies and for informing future trials’ design. Nevertheless, such an approach may be limited, for example, by the availability of RWD that matches the target trials of interest, and further investigations are warranted.

Abstract Background Despite improved survival rates, cancer survivors are experiencing worse health outcomes with complications of treatment, such as type 2 diabetes mellitus (T2D), that may deteriorate survivorship. The purpose of this review was to provide a comprehensive review of T2D incidence following cancer diagnosis. Methods: The study included: (1) cohort studies, (2) cancer diagnosis by a doctor, (3) incidence of T2D after diagnosis of cancer, and (4) adult patients over 18 years. Studies that focused on patients who had T2D as a preexisting condition at cancer diagnosis were excluded. Results: Of a total of 16 studies, overall incidence of T2D ranged from 5.4% to 55.3%. The highest T2D incidence rate was observed in colorectal patients with cancer (53%). While results in prostate patients with cancer were mixed, patients who underwent androgen deprivation therapy (ADT) had a significantly higher incidence of new‐onset T2D (12.8%, p = 0.01). Patients treated with chemotherapy within 1–5 years of initial diagnosis of colorectal cancer were at approximately 30% higher risk of T2D. One study found that 48% of T2D was preventable with optimal management during the process of patient care. Conclusion: Blood glucose management may allow physicians to intervene early and improve outcomes among patients with cancer.

Abstract Clinical studies, especially randomized, controlled trials, are essential for generating evidence for clinical practice. However, generalizability is a long‐standing concern when applying trial results to real‐world patients. Generalizability assessment is thus important, nevertheless, not consistently practiced. We performed a systematic review to understand the practice of generalizability assessment. We identified 187 relevant articles and systematically organized these studies in a taxonomy with three dimensions: (i) data availability (i.e., before or after trial (a priori vs. a posteriori generalizability)); (ii) result outputs (i.e., score vs. nonscore); and (iii) populations of interest. We further reported disease areas, underrepresented subgroups, and types of data used to profile target populations. We observed an increasing trend of generalizability assessments, but

Abstract Background Disparities exist among patients with pancreatic ductal adenocarcinoma (PDAC). Non‐White race is regarded as a negative predictor of expected treatment and overall survival. Data suggest that Academic Research Programs (ARP) provide better outcomes for minorities, but ethnic/minority outcomes are underreported. We hypothesize that outcomes among racially/ethnically diverse PDAC patients may be influenced by treatment facility. Methods The National Cancer Database was used to identify 170,327 patients diagnosed with PDAC between 2004 and 2015. Cox proportional‐hazard regression was used to compare survival between race/ethnic groups across facilities. Results In unadjusted models, compared to non‐Hispanic Whites (NHW), non‐Hispanic Blacks (NHB) had the worst overall survival (HR = 1.05, 95%CI: 1.03‐1.06, P

Abstract Introduction: Racial disparities in colorectal cancer (CRC) can be addressed through increased adherence to screening guidelines. In real-life encounters, patients may be more willing to follow screening recommendations delivered by a race concordant clinician. The growth of telehealth to deliver care provides an opportunity to explore whether these effects translate to a virtual setting. The primary purpose of this pilot study is to explore the relationships between virtual clinician (VC) characteristics and CRC screening intentions after engagement with a telehealth intervention leveraging technology to deliver tailored CRC prevention messaging. Methods: Using a posttest-only design with three factors (VC race-matching, VC gender, intervention type), participants (N = 2267) were randomised to one of eight intervention treatments. Participants self-reported perceptions and behavioral intentions. Results: The benefits of matching participants with a racially similar VC trended positive but did not reach statistical significance. Specifically, race-matching positively influenced screening intentions for Black participants but not for Whites (b = 0.29, p = 0.10). Importantly, perceptions of credibility, attractiveness, and message relevance significantly influenced screening intentions and the relationship with race-matching. Conclusions: To reduce racial CRC screening disparities, investments are needed to identify patient-focused interventions to address structural barriers to screening. This study suggests that telehealth interventions that match Black patients with a Black VC can enhance perceptions of credibility and message relevance, which may then improve screening intentions. Future research is needed to examine how to increase VC credibility and attractiveness, as well as message relevance without race-matching.

Cancer is a major health problem in the U.S and type 2 diabetes mellitus (T2DM) is known to increase the risk for the development of many cancers. Metformin, a first-line therapy for treating T2DM, is increasingly being used for its anticancer effects; however, the literature is limited on the effect of metformin dose on overall survival in patients with stage IV cancer. Overall survival was defined as the time interval from the date of diagnosis to the last known follow-up or death from any cause. Subjects who were alive on December 31, 2016 were censored. In this cohort study we examined the relationship between metformin dose and overall survival in persons with both T2DM and stage IV lung, breast, colorectal, prostate, or pancreas cancers. We used a retrospective study design with Cox proportional hazards regression analysis of the 2007–2016 of the Surveillance Epidemiology and End Results-Medicare (SEER) dataset. Of the 7,725 patients, 2,981(38.5%) had been prescribed metformin. Patients who used metformin had significantly better overall survival in both unadjusted (Unadjusted HR, 0.73; 95% CI, 0.69–0.76; p < 0.001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73–0.81; p < 0.001). The overall survival between patients who took metformin with average daily dose ≥ 1000mg or < 1000mg were not statistically significant (aHR, 1.00; 95% CI, 0.93–1.08; p = 0.90). Metformin use regardless of dose is associated with increased overall survival in older adults with stage IV cancer.

The prevalence of primary liver cancer is rapidly rising all around the world. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Unfortunately, the traditional treatment methods to cure HCC showed poor efficacy in patients who are not candidates for liver transplantation. Until recently, tyrosine kinase inhibitors (TKIs) were the front-line treatment for unresectable liver cancer. However, rapidly emerging new data has drastically changed the landscape of HCC treatment. The combination treatment of atezolizumab plus bevacizumab (immunotherapy plus anti-VEGF) was shown to provide superior outcomes and has become the new standard first-line treatment for unresectable or metastatic HCC. Currently, ongoing clinical trials with immune checkpoint blockade (ICB) have focused on assessing the benefit of antibodies against programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4) as monotherapies or combination therapies in patients with HCC. In this review, we briefly discuss the mechanisms underlying various novel immune checkpoint blockade therapies and combination modalities along with recent/ongoing clinical trials which may generate innovative new treatment approaches with potential new FDA approvals for HCC treatment in the near future.

Abstract Background 5-Fluorouracil (5-FU) is an antimetabolite chemotherapy used for a variety of solid tumors. It has the potential to cause a wide spectrum of cardiotoxicity, ranging from asymptomatic electrocardiographic changes to cardiomyopathy and subsequent cardiac failure. Main body of the abstract: We present two descriptive cases of new-onset severe cardiomyopathy induced by 5-FU followed by a review of the literature. Conclusion Our case series emphasizes the importance of early recognition of this rare complication and prompt cessation of 5-FU, as cardiac dysfunction in this context is potentially reversible.

Abstract Background Unintentional weight loss is a major problem for patients with gastrointestinal (GI) cancers because it affects treatment, survival outcomes, and quality of life. To date, little is known about the trajectory of weight loss and the relationship between baseline body mass index (BMI), location of the cancer, and outcomes. The aims of this study were to investigate patterns of weight loss over time in patients with GI cancer according to BMI groups (low, normal, and high) and location of cancer. Methods We examined de‐identified electronic medical record data of 801 adults (>21 years) with GI cancer using ICD‐9 codes (150–159). Descriptive statistics and linear mixed models were used to examine unintentional weight loss over time by BMI group (low, normal, and high) and to determine the effect of primary cancer site and patient characteristics on weight loss. Results The mean age of patients was 66.5 ± 11.9 years (21–95 years), with 58% male and 86% White. Mean weight loss over 3 years was 21.39 kg. At the first observation point, 7.8% were in the low BMI group, 30.1% were in the normal, and 62% were in the high group. At the end of observation, a majority of deaths (35.5%) occurred in the low BMI group (BMI

Abstract Pancreatic cancer (PC) is characterized by racial/ethnic disparities and the debilitating muscle‐wasting condition, cancer cachexia. Florida ranks second in the number of PC deaths and has a large and understudied minority population. We examined the primary hypothesis that PC incidence and mortality rates may be highest among Black Floridians and the secondary hypothesis that biological correlates of cancer cachexia may underlie disparities. PC incidence and mortality rates were estimated by race/ethnicity, gender, and county using publicly available state‐wide cancer registry data that included approximately 2700 Black, 25 200 Non‐Hispanic White (NHW), and 3300 Hispanic/Latino (H/L) Floridians diagnosed between 2004 and 2014. Blacks within Florida experienced a significantly (P

While patients with resectable pancreatic ductal adenocarcinoma (PDAC) show improved survival compared to their non-resectable counterparts, survival remains low owing to occult metastatic disease and treatment resistance. Liquid biopsy based on circulating tumor cells (CTCs) and cell-free DNA (cfDNA) has been shown to predict recurrence and treatment resistance in various types of cancers, but their utility has not been fully demonstrated in resectable PDAC. We have simultaneously tracked three circulating biomarkers, including CTCs, cfDNA, and circulating tumor DNA (ctDNA), over a period of cancer treatment using a microfluidic device and droplet digital PCR (ddPCR). The microfluidic device is based on the combination of filtration and immunoaffinity mechanisms. We have measured CTCs, cfDNA, and ctDNA in a cohort of seven resectable PDAC patients undergoing neoadjuvant therapy followed by surgery, and each patient was followed up to 10 time points over a period of 4 months. CTCs were detectable in all patients (100%) at some point during treatment but were detectable in only three out of six patients (50%) prior to the start of treatment. Median cfDNA concentrations remained comparable to negative controls throughout treatment. ddPCR was able to find KRAS mutations in six of seven patients (86%); however, these mutations were present in only two of seven patients (29%) prior to treatment. Overall, the majority of circulating biomarkers (81% for CTCs and 91% for cfDNA/ctDNA) were detected after the start of neoadjuvant therapy but before surgery. This study suggests that a longitudinal study of circulating biomarkers throughout treatment provides more useful information than those single time-point tests for resectable PDAC patients.

Gastrointestinal stromal tumors (GISTs) are rare tumors of gastrointestinal (GI) tract with mesenchymal cell origin. Extragastrointestinal stromal tumors (EGISTs) are unusual tumors that exhibit the same immunohistochemical and genetic abnormalities as GISTs and most commonly affect the omentum and mesentery. EGISTs of the pelvis and the female reproductive system are exceedingly rare and a frequent diagnostic pitfall. In this report, we present two cases of EGISTs along with a review of the literature. Keywords: Extragastrointestinal stromal tumor, Vagina, Pelvic cavity

Abstract Background Cancer is the second leading cause of death in the United States, exceeded only by heart disease. Extant cancer survival analyses have primarily focused on individual-level factors due to limited data availability from a single data source. There is a need to integrate data from different sources to simultaneously study as much risk factors as possible. Thus, we proposed an ontology-based approach to integrate heterogeneous datasets addressing key data integration challenges. Methods Following best practices in ontology engineering, we created the Ontology for Cancer Research Variables (OCRV) adapting existing semantic resources such as the National Cancer Institute (NCI) Thesaurus. Using the global-as-view data integration approach, we created mapping axioms to link the data elements in different sources to OCRV. Implemented upon the Ontop platform, we built a data integration pipeline to query, extract, and transform data in relational databases using semantic queries into a pooled dataset according to the downstream multi-level Integrative Data Analysis (IDA) needs. Results Based on our use cases in the cancer survival IDA, we created tailored ontological structures in OCRV to facilitate the data integration tasks. Specifically, we created a flexible framework addressing key integration challenges: (1) using a shared, controlled vocabulary to make data understandable to both human and computers, (2) explicitly modeling the semantic relationships makes it possible to compute and reason with the data, (3) linking patients to contextual and environmental factors through geographic variables, (4) being able to document the data manipulation and integration processes clearly in the ontologies. Conclusions Using an ontology-based data integration approach not only standardizes the definitions of data variables through a common, controlled vocabulary, but also makes the semantic relationships among variables from different sources explicit and clear to all users of the same datasets. Such an approach resolves the ambiguity in variable selection, extraction and integration processes and thus improve reproducibility of the IDA.

Abstract Background Access to direct-to-consumer genetic testing services has increased in recent years. However, disparities in knowledge and awareness of these services are not well documented. We examined awareness of genetic testing services by rural/urban and racial/ethnic status. Methods Analyses were conducted using pooled cross-sectional data from 4 waves (2011–2014) of the Health Information National Trends Survey (HINTS). Descriptive statistics compared sample characteristics and information sources by rural/urban residence. Logistic regression was used to examine the relationship between geography, racial/ethnic status, and awareness of genetic testing, controlling for sociodemographic characteristics. Results Of 13,749 respondents, 16.7% resided in rural areas, 13.8% were Hispanic, and 10.1% were non-Hispanic black. Rural residents were less likely than urban residents to report awareness of genetic testing (OR = 0.74, 95% CI = 0.63–0.87). Compared with non-Hispanic whites, racial/ethnic minorities were less likely to be aware of genetic testing: Hispanic (OR = 0.68, 95% CI = 0.56–0.82); and non-Hispanic black (OR = 0.74, 95% CI = 0.61–0.90). Conclusions Rural-urban and racial-ethnic differences exist in awareness of direct-to-consumer genetic testing. These differences may translate into disparities in the uptake of genetic testing, health behavior change, and disease prevention through precision and personalized medicine.

Objectives: CVS, the largest US pharmacy chain, discontinued selling tobacco products in 2014; meanwhile, Family Dollar and Dollar General, the two largest dollar store chains, began selling tobacco in 2012 and 2013, respectively. The purpose of this study is to evaluate the differential change in tobacco retailer density (TRD) by rurality throughout 12 Southeastern US states. Methods: Tobacco retailer density was calculated for CVS and dollar store locations and combined to represent retailer density change before and after policy changes. Bivariate analyses were conducted to compare the corporate-initiated changes in county-level retailer density across rurality categories. Results: Findings suggest a statistically significant difference (p

Introduction: Patients with gastrointestinal (GI) cancer-associated cachexia are at risk of high morbidity and mortality. This randomized single-blind pilot study compared the complementary use of targeted acupuncture (TA) with nontargeted acupuncture (NTA) for halting cachexia symptoms. Methods: GI cancer patients with cachexia undergoing chemotherapy were assigned to receive 8 weekly sessions of either TA (n = 15) or NTA (n = 15) following a specific acupuncture protocol. Bioelectrical impedance analysis and weight were measured weekly. Biological markers, including C-reactive protein, prealbumin, tumor necrosis factor-α, lactate dehydrogenase (LDH), leptin, and ghrelin blood levels were determined at specific intervals. Results: Prealbumin levels and fat-free mass were significantly higher in the NTA group at the end of the study, but remained stable in TA group. TA group had significantly lower (230 IU/L vs 288 IU/L, P = .04) LDH at the end of the study, but elevated tumor necrosis factor-α levels (13.15 pg/mL vs 9.24 pg/mL, P = .04). The absolute blood leptin and ghrelin levels decreased in the TA but remained stable in the NTA group. Both groups maintained weight, but the TA group trended toward weight gain during the last 2 weeks of the study. No adverse events related to acupuncture were reported. Conclusions: TA using predetermined, reproducible points may provide benefits to some patients with GI cancer cachexia by normalizing metabolic dysregulation. Elevated ghrelin levels are indicative of insulin resistance, which can lead to increased muscle loss represented by increased LDH activity in the NTA group. The pilot study provided completion rate and effect size for the primary outcome measures for a larger study. A longer treatment duration may be required to further refine these findings.

BackgroundSocial determinants of health (SDoH), such as geographic neighborhoods, access to health care, education, and social structure, are important factors affecting people’s health and health outcomes. The SDoH of patients are scarcely documented in a discrete format in electronic health records (EHRs) but are often available in free-text clinical narratives such as physician notes. Innovative methods like natural language processing (NLP) are being developed to identify and extract SDoH from EHRs, but it is imperative that the input of key stakeholders is included as NLP systems are designed. ObjectiveThis study aims to understand the feasibility, challenges, and benefits of developing an NLP system to uncover SDoH from clinical narratives by conducting interviews with key stakeholders: (1) oncologists, (2) data analysts, (3) citizen scientists, and (4) patient navigators. MethodsIndividuals who frequently work with SDoH data were invited to participate in semistructured interviews. All interviews were recorded and subsequently transcribed. After coding transcripts and developing a codebook, the constant comparative method was used to generate themes. ResultsA total of 16 participants were interviewed (5 data analysts, 4 patient navigators, 4 physicians, and 3 citizen scientists). Three main themes emerged, accompanied by subthemes. The first theme, importance and approaches to obtaining SDoH, describes how every participant (n=16, 100%) regarded SDoH as important. In particular, proximity to the hospital and income levels were frequently relied upon. Communication about SDoH typically occurs during the initial conversation with the oncologist, but more personal information is often acquired by patient navigators. The second theme, SDoH exists in numerous forms, exemplified how SDoH arises during informal communication and can be difficult to enter into the EHR. The final theme, incorporating SDoH into health services research, addresses how more informed SDoH can be collected. One strategy is to empower patients so they are aware about the importance of SDoH, as well as employing NLP techniques to make narrative data available in a discrete format, which can provide oncologists with actionable data summaries. ConclusionsExtracting SDoH from EHRs was considered valuable and necessary, but obstacles such as narrative data format can make the process difficult. NLP can be a potential solution, but as the technology is developed, it is important to consider how key stakeholders document SDoH, apply the NLP systems, and use the extracted SDoH in health outcome studies.

BackgroundAccrual to oncology clinical trials remains a challenge, particularly during the COVID-19 pandemic. For late phase clinical trials funded by the National Cancer Institute, the development of these research protocols is a resource-intensive process; however, mechanisms to optimize patient accrual after trial activation are underdeveloped across the National Clinical Trial Network (NCTN). Low patient accrual can lead to the premature closure of clinical trials and can ultimately delay the availability of new, potentially life-saving therapies in oncology. ObjectiveThe purpose of this study is to formally create an easily implemented tool kit of resources for investigators of oncology clinical trials within the NCTN, specifically the NRG Oncology cooperative group, in order to optimize patient accrual. MethodsNRG Oncology sought to formally develop a tool kit of resources to use at specific time points during the lifetime of NRG Oncology clinical trials. The tools are clearly described and involve the facilitation of engagement of the study principal investigator with the scientific and patient advocate community during the planning, activation, and accrual periods. Social media tools are also leveraged to enhance such engagement. The principal investigator (PI) tool kit was created in 2019 and thereafter piloted with the NRG Oncology/Alliance NRG-LU005 phase II or III trial in small-cell lung cancer. The PI tool kit was developed by the NRG Oncology Protocol Operations Management committee and was tested with the NRG/Alliance LU005 randomized trial within the NCTN. ResultsNRG Oncology/Alliance NRG-LU005 has seen robust enrollment, currently 127% of the projected accrual. Importantly, many of the tool kit elements are already being used in ongoing NRG Oncology trials, with 56% of active NRG trials using at least one element of the PI tool kit and all in-development trials offered the resource. This underscores the feasibility and potential benefits of deploying the PI tool kit across all NRG Oncology trials moving forward. ConclusionsWhile clinical trial accrual can be challenging, the PI tool kit has been shown to augment accrual in a low-cost and easily implementable fashion. It could be widely and consistently deployed across the NCTN to improve accrual in oncology clinical trials. Trial RegistrationClinicalTrials.gov NCT03811002; https://clinicaltrials.gov/ct2/show/NCT03811002

Cancer is a major health problem in the U.S and type 2 diabetes mellitus (T2DM) is known to increase the risk for the development of many cancers. Metformin, a first-line therapy for treating T2DM, is increasingly being used for its anticancer effects; however, the literature is limited on the effect of metformin dose on overall survival in patients with stage IV cancer. Overall survival was defined as the time interval from the date of diagnosis to the last known follow-up or death from any cause. Subjects who were alive on December 31, 2016 were censored. In this cohort study we examined the relationship between metformin dose and overall survival in persons with both T2DM and stage IV lung, breast, colorectal, prostate, or pancreas cancers. We used a retrospective study design with Cox proportional hazards regression analysis of the 2007-2016 of the Surveillance Epidemiology and End Results-Medicare (SEER) dataset. Of the 7,725 patients, 2,981(38.5%) had been prescribed metformin. Patients who used metformin had significantly better overall survival in both unadjusted (Unadjusted HR, 0.73; 95% CI, 0.69-0.76; p < 0.001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; p < 0.001). The overall survival between patients who took metformin with average daily dose ≥ 1000mg or < 1000mg were not statistically significant (aHR, 1.00; 95% CI, 0.93-1.08; p = 0.90). Metformin use regardless of dose is associated with increased overall survival in older adults with stage IV cancer.

BackgroundTraditionally, promotion of colorectal cancer (CRC) screening among Black men was delivered by community health workers, patient navigators, and decision aids (printed text or video media) at clinics and in the community setting. A novel approach to increase CRC screening of Black men includes developing and utilizing a patient-centered, tailored message delivered via virtual human technology in the privacy of one’s home. ObjectiveThe objective of this study was to incorporate the perceptions of Black men in the development of a virtual clinician (VC) designed to deliver precision messages promoting the fecal immunochemical test (FIT) kit for CRC screening among Black men in a future clinical trial. MethodsFocus groups of Black men were recruited to understand their perceptions of a Black male VC. Specifically, these men identified source characteristics that would enhance the credibility of the VC. The modality, agency, interactivity, and navigability (MAIN) model, which examines how interface features affect the user’s psychology through four affordances (modality, agency, interactivity, and navigability), was used to assess the presumed credibility of the VC and likability of the app from the focus group transcripts. Each affordance triggers heuristic cues that stimulate a positive or a negative perception of trustworthiness, believability, and understandability, thereby increasing source credibility. ResultsIn total, 25 Black men were recruited from the community and contributed to the development of 3 iterations of a Black male VC over an 18-month time span. Feedback from the men enhanced the visual appearance of the VC, including its movement, clothing, facial expressions, and environmental surroundings. Heuristics, including social presence, novelty, and authority, were all recognized by the final version of the VC, and creditably was established. The VC was named Agent Leveraging Empathy for eXams (ALEX) and referred to as “brother-doctor,” and participants stated “wanting to interact with ALEX over their regular doctor.” ConclusionsInvolving Black men in the development of a digital health care intervention is critical. This population is burdened by cancer health disparities, and incorporating their perceptions in telehealth interventions will create awareness of the need to develop targeted messages for Black men.

Introduction: Colonoscopy screening is an effective method of detecting and preventing colorectal cancer. Standard procedure for most colonoscopies (98%) is to use conscious sedation, which can cause short-term cognitive impairment postprocedure, including communication difficulties. In this study, we explored providers’ (gastroenterology doctors and nurses) perceptions of the barriers to optimal communication with patients immediately following colonoscopy. Methods: We conducted interviews with 61 providers across 5 clinical configurations. Interviews were transcribed and coded with NVivo version 11 software. Results: Themes emerged regarding barriers to optimal provider–patient communication postcolonoscopy: patient barriers (sedation and patient characteristics), caregiver barriers, and system characteristics. Conclusions: Providers’ perceived barriers to communication are an important topic to study. They endorsed, in particular, interventions that target the postcolonoscopy time frame when patients may still be sedated, but providers must convey important discharge and follow-up instructions.