Freenome (United States)

BackgroundEmerging blood tests may improve colorectal cancer (CRC) screening uptake and outcomes but are less sensitive for advanced precancerous lesions than some currently recommended tests. We examine whether these tests meet expectations for the US Preventive Services Task Force (USPSTF) recommendation.MethodsA decision-analytic model that informed USPSTF was replicated and used to estimate the lifetime benefits (averted CRC cases and deaths, life-years gained [LYG]), burdens (required screening tests and colonoscopies), and harms (colonoscopy-related complications) for annual, biennial, or triennial blood testing through age 45-75 years vs a benchmark of recommended and contemporary stool-based strategies, with colonoscopy screening as the reference. Base-case analyses assumed 100% adherence. Sensitivity analyses evaluated more realistic scenarios.ResultsAmong benchmark strategies, colonoscopy screening had the most benefit, with an estimated 30 CRC deaths averted, 356 LYG, 4270 colonoscopies required, and 15 complications per 1000 adults; stool-based strategies resulted in 81% to 88% of LYG for colonoscopy, 6829-19 476 screening tests, 1523-1880 colonoscopies, and 9-10 complications. By comparison, annual blood testing resulted in 85% to 87% of LYG for colonoscopy and an intermediate number of screenings, colonoscopies, and complications. Biennial and triennial blood testing provided 57% to 72% of LYG for colonoscopy but resulted in net population benefit under plausible scenarios for increased utilization vs existing strategies.ConclusionsThe estimated benefits, burdens, and harms of annual blood testing are within the range of current CRC screening strategies. Biennial and triennial testing should also be considered for recommendation given the potential for increased utilization and net population benefit.

Data will be made available upon reasonable request to the corresponding author.

In recent years, there has been a surge in the development of new, blood-based, single- and multi-cancer detection tests (SCD and MCD), which can detect cancer signals prior to the onset of symptoms or clinical diagnosis of cancer. Recognizing the need for consensus definitions and standardized evidence development frameworks for these new types of blood tests, the Early Detection and Screening Working Group of the Blood Profiling Atlas in Cancer Consortium, a collaborative initiative dedicated to advancing standards and best practices, developed and published a lexicon for liquid biopsy–based SCD and MCD tests. During the preparation of the lexicon, the group recognized challenges with regard to the definitions of key terms and concepts describing absolute and RR assessment of intended use populations for cancer screening tests. This article captures the working group’s discussions on (i) risk assessment including considerations for adapting historical SCD risk terminology like “average risk” and “elevated risk” to MCD tests, (ii) the implications of this terminology for describing intended use populations, and (iii) the existing gaps in evidence for determination of absolute risks.

Recent improvements in proteomics technologies have fundamentallyaltered our capacities to characterize human biology. There is anever-growing interest in using these novel methods for studying thecirculating proteome, as blood offers an accessible window into humanhealth. However, every methodological innovation and analytical progresscalls for reassessing our existing approaches and routines to ensurethat the new data will add value to the greater biomedical researchcommunity and avoid previous errors. As representatives of HUPO’sHuman Plasma Proteome Project (HPPP), we present our 2024 survey ofthe current progress in our community, including the latest buildof the Human Plasma Proteome PeptideAtlas that now comprises 4608proteins detected in 113 data sets. We then discuss the updates ofestablished proteomics methods, emerging technologies, and investigationsof proteoforms, protein networks, extracellualr vesicles, circulatingantibodies and microsamples. Finally, we provide a prospective viewof using the current and emerging proteomics tools in studies of circulatingproteins.

Oily fish is a major dietary source of omega-3 polyunsaturated fatty acids and other nutrients that may have a positive effect on bone health. However, this association is inconsistent and seems to be more evident in certain ethnic groups. We aimed to assess the association between oily fish intake and bone mineral density (BMD) in frequent fish consumers of Amerindian ancestry living in rural Ecuador. This study included 399 individuals aged ≥ 60years living in three neighboring rural villages of coastal Ecuador. Dietary oily fish intake was quantified systematically using validated surveys and BMD was determined by dual-energy x-ray absorptiometry. Ordinal logistic regression models, adjusted for demographics and cardiovascular risk factors, were fitted to assess the independent association between oily fish intake and bone health. Participants had a mean age of 68.8 ± 6.8years, and 58% were women. The mean intake of oily fish was 8.5 ± 4.7 servings/week, with 308 (77%) reporting high fish intake (≥ 5.2 servings/week [728g]). Ninety-four (24%) participants had normal BMD T-scores, 149 (37%) had osteopenia, and 156 (39%) had osteoporosis. Ordinal logistic regression models showed no association between high fish intake and bone health in the total population. When men and women were analyzed separately, the association became significant for women only in both unadjusted (OR: 2.52; 95% C.I.: 1.22 - 5.23) and fully-adjusted models (OR: 2.23; 95% C.I.: 1.03 - 4.81). Consumption of ≥ 5.2 oily fish servings/week is associated with lower prevalence of osteopenia and osteoporosis in elderly women of Amerindian ancestry.

Abstract Noninvasive monitoring of cancer shows great promise in assessing therapy response and improving patient outcomes. Recently, various groups have developed methods that detect circulating tumor DNA (ctDNA) in the plasma to measure minimal or molecular residual disease (MRD). Aberrant DNA methylation patterns are a hallmark of cancers, and robust signals can be detected by sensitive ctDNA assays. Here, we present a methylation-based approach for longitudinal monitoring of tumor burden that is tumor-naive, i.e., with no reliance on prior characterization of tumor molecular characteristics. We assess the effectiveness of our approach in a cohort of colorectal cancer (CRC) patients receiving chemotherapy with or without additional targeted agents. Longitudinal blood samples were collected from patients (n = 57) while on therapy, which averaged 4.9 months, for a total of 239 sample collection time points (median per patient = 5). Based on RECIST status, 16 patients were classified as complete responders (CR) at the end of treatment. We generated plasma cell free DNA-derived libraries for methylation sequencing targeting regions relevant to CRC. Next, we computed a disease burden score for each sample and related these scores to clinical response (CR vs. non-CR). We trained a classifier on an independent cohort of CRC and healthy donor plasma cfDNA samples, and used this classifier to check for residual disease at the end of treatment for each of our 57 patients. The classifier detected residual disease in only 3/16 CRs (19%) but 35/41 non-CRs (85%). Two of the non-CR patients were initially assessed as CRs at earlier time points. In both cases, our method successfully detected residual disease at or prior to the CR assessment and consistently showed residual disease in all follow up samples. This suggests improved sensitivity relative to RECIST and highlights the potential of using noninvasive blood tests for continuous monitoring of CRC patients receiving therapy. Citation Format: Alison D. Tang, Rebecca Gupte, Victoria Cheung, Tao Qing, Austin Cauwels, Emily Leff, Kimberly Walter, Ehsan Tabari, Alex Lovejoy, Jimmy C. Lin. Noninvasive longitudinal monitoring of residual disease in chemotherapy-treated colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4788.

Street violence has detrimental effects on cardiovascular health (CVH). However, the significance of these consequences have not been systematically evaluated. In this study, we aimed to assess the impact of fear of crime on CVH status among community-dwellers aged ≥40 years living in a rural village stricken by violence. Participants were selected from individuals enrolled in the Atahualpa Project Cohort, a population-based longitudinal study that aims to reduce the burden of cardiovascular risk factors and diseases in rural Ecuador. Fear of crime was evaluated using a structured scale. The Life's Simple 7 construct of the American Heart Association was employed to assess CVH before the escalation of violence and crime in the village (2019) and at the end of the study (2024). Multivariate logistic regression models were fitted to examine the association between the exposure and outcomes. A total of 648 individuals (mean age = 57.4 ± 11.7 years; 56% women) were included. At the end of the follow-up, significant association between fear of crime levels and worsening CVH status was noted. Participants allocated to the second and third tertiles of fear of crime were 3.27 (95% CI = 2.07-5.19) and 5.46 (95% CI = 3.14-9.48) times more likely to have worsening CVH status at follow-up compared to baseline determinations, respectively. This study shows an aggravating impact of fear of crime on the CVH status and identifies interventional targets that may help to reduce the risk of CVH status worsening in community-dwellers living in rural settings afflicted by violence.