Citations

Hand impairment is a frequently reported complaint in systemic sclerosis (SSc) patients and a leading cause of disability and diminished quality of life. Managing hand pain can be particularly challenging due to the coexistence of non-inflammatory arthralgias, inflammatory arthritis, acro-osteolysis, tenosynovitis, joint contractures, tendon friction rubs, nerve entrapment, Raynaud’s phenomenon (RP), digital ulcers (DU), sclerodactyly, calcinosis, and chronic pain. While physical examination and radiographs are the first line methods for evaluating hand pain, they are limited in scope and miss many underlying etiologies of hand impairment. We propose a joint ultrasound (US) hand protocol to differentiate between various articular, periarticular, ischemic, skin, and nerve pathologies and to assist in targeted treatment strategies.

ABSTRACT Objective: The aim of the study is to develop a predictive model for in-hospital mortality in critically ill patients with cirrhosis and sepsis, using clinical and laboratory data. Design: This is a retrospective cohort study. Setting: Medical and mixed intensive care units (ICUs) of a tertiary medical center. Patients: Cirrhotic adults were admitted with sepsis to the ICUs from January of 2007 to May of 2017. Interventions: None. Measurements and Main Results: Of 2,595 ICU admissions of patients with cirrhosis, 277 with first ICU admission for sepsis were included in the analysis, and 37% died in the hospital. Patients who stayed in the ICU for at least 6 h (n = 275) were considered for the multivariate model. Ten-fold cross-validation was used to estimate best parameter values and model performance, and the final model was chosen as the model maximizing area under the receiver-operating characteristic curve. Variables in order of impact were Acute Physiology and Chronic Health Evaluation (APACHE) III score, initial serum lactate, conjugated bilirubin, serum creatinine, model for end-stage liver disease score, age, body mass index, and serum hemoglobin. The final best model from cross-validation presented an area under the receiver operator characteristic curve (AUC) of 0.75, using a cut-point of 50% estimated probability, sensitivity and specificity were 0.46 and 0.90, respectively, with positive predictive value of 0.72 and negative predictive value of 0.74. These results were similar to the APACHE III only model (AUC = 0.74, sensitivity = 0.43, specificity = 0.89, positive predictive value = 0.69, negative predictive value = 0.73). Conclusion: The combination of initial serum lactate level, conjugated bilirubin, initial serum creatinine, model for end-stage liver disease score, age, body mass index, and serum hemoglobin did not yield meaningful improvement in the AUC and did not provide advantage over the APACHE III score for the prediction of in-hospital mortality in critically ill patients with cirrhosis and sepsis.

Abstract Background: It is a common practice to monitor trastuzumab-related cardiac toxicity (TRCT) using left ventricular ejection fraction (LVEF) in patients who receive trastuzumab-containing therapy for human epidermal growth factor receptor 2 (HER2)-positive cancers. However, this monitoring approach does not appear cost effective in patients with HER2-positive gastrointestinal (GI) cancers given poor overall survival (OS). Here, we aim to examine the incidence of clinically significant TRCT in this target population. Methods: This is a retrospective cohort study of patients with advanced HER2-positive GI cancers who received trastuzumab-containing therapies (trastuzumab +/- pertuzumab, chemotherapy +/- immunotherapy + trastuzumab, trastuzumab deruxtecan) between 2011 and 2023. HER2 status was determined by immunohistochemistry, fluorescent in situ hybridization, and/or next generation sequencing. LVEF was estimated by serial transthoracic echocardiograms (TTE). Continuous variables were summarized as median and interquartile range (IQR). Paired Wilcoxon signed rank test was used to compare serial LVEF. OS was estimated using Kaplan-Meier method. Results: A total of 243 patients were included in this study with a median age of 64 (IQR: 55-70) years. 139 (57%) patients had esophageal or GEJ adenocarcinoma; 45 (19%) patients had gastric cancer; 37 (15%) patients had colorectal cancer; and the rest had other GI cancers. Median follow-up time was 18.6 (IQR: 9.2-36) months. Median OS from cancer diagnosis and the first dose of trastuzumab-containing therapy were 24.1 (95%CI: 20.2-30.2) and 11.7 (95%CI: 10.4-15.6) months, respectively. Patients received a median of 13 cycles of trastuzumab-containing therapy for a median duration of 4.1 (IQR: 1.4-10.1) months. The median number of TTE each patient had throughout therapy was 2 (IQR: 1-4). Median baseline LVEF was 61% (IQR: 56-65%) which was significantly higher (p<0.001) than the median lowest LVEF of 58% (IQR: 53-62%) during therapy, but not different (p=0.14) from the most recent median LVEF of 60% (IQR: 56-64%) after discontinuation of trastuzumab. Among 176 patients with serial LVEF data, 16 (9%) had > 10% LVEF drop; 7 (44%) of these 16 patients had LVEF recovery. None of the cardiovascular risk factors prior to trastuzumab treatment including hypertension, diabetes, hyperlipidemia, peripheral arterial disease, coronary artery disease, and stroke were significantly associated with the development of TRCT. Conclusion: The incidence of clinically significant LVEF drop appears low in patients with advanced GI cancers as post-treatment LVEF recovery to baseline was observed at the population level. The value of using TTE to monitor TRCT in these patients with short OS should be further assessed in the perspective of cost effectiveness. Citation Format: Samual R. Kosydar, Matteo Castrichini, Mojun Zhu, Hao Xie. The value of routine trastuzumab-related cardiac toxicity monitoring in gastrointestinal cancers [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 6298.

Abstract Prostate cancer, impacts over 3.1 million survivors, poses persistent challenges in post-treatment care, creating uncertainties regarding the best course of follow-up actions for leading productive lives. Unfortunately, these concerns, especially among ethnically diverse Black men, are frequently overlooked. The post-treatment journey for Black prostate cancer survivors is dependent on how they navigate survivorship to determine how it impacts their quality of life and emotional wellbeing. This study evaluated the post-treatment cancer experience and gauge satisfaction with care among a cohort of Black survivors (n = 45). Utilizing data from the 2023 National Coalition for Cancer Survivorship State of Survivorship Study (n = 1303), conducted between May 9th to June 6th, 2023, the research specifically targets self-identified Black males, constituting 10% of the study population and spanning an age range from 18 to 80 years. Results revealed that oncologists (44%) managed post-treatment care more than primary care physicians (30%). While conversation about follow-up care monitoring cancer tests regularly occurred (68%), while topics such as quality of life (27%), mental and emotional health (21%), and post-treatment survivorship care plans (9%) received minimal attention. Although most survivors felt generally informed about side effects (62% very informed), less than half felt their health care team was very helpful in dealing with them. Symptoms reported by survivors included feeling overly tired (47%), depression, anxiety, and mental health impacts (40%), and uncertainty about the cancer status (34%). Survivors engaging in diverse integrative treatments, including such practices as prayer and exercise, represented 29% and 28%, respectfully. Notably, 80% and 60% of individuals utilizing these modalities reported finding them effective during the post-treatment care phase. The journey from the point of prostate cancer diagnosis to post-treatment can impose a significant mental and physical toll on survivors. To address the emotional and psychological challenges associated with a diagnosis and post-treatment, survivors adopting integrative oncology modalities and exercise prescriptions to cope are crucial. These strategies may help survivors maintain a positive outlook and achieve optimal post-treatment health, with a focus on providing tailored resources that cater to the unique needs of Black survivors. Citation Format: Dottington Fullwood, Daniel Lee, Veronika Panagiotou, Samantha B. Siegel, Mariel Molina, Folakemi T. Odedina. Understanding survivorship: A national survey of post-treatment experiences in Black prostate cancer survivors [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 7447.

Abstract Background: The impact of a prior history of non-hematologic malignancy (NHM) on clinical outcomes among individuals with newly diagnosed chronic lymphocytic leukemia (CLL) or monoclonal B-cell lymphocytosis (MBL), the precursor to CLL, is not well known. Methods: In this prospective study, we identified individuals with CLL/MBL who were seen in the Division of Hematology at the Mayo Clinic, Rochester. Participants provided consent within nine months of diagnosis, had no prior history of hematological malignancy, and completed a self-reported risk-factor questionnaire, including a prior history of NHM. Time to first treatment (TTFT) was defined as the time between the date of diagnosis and the earliest date of the first CLL treatment, death, or the last known treatment-free follow-up date. Overall survival (OS) was defined as the time from diagnosis to death or the last follow-up. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between a prior history of a NHM with OS and TTFT. We adjusted for sex and the CLL International Prognostic Index (CLL-IPI), a score comprised of five key CLL prognostic factors, including age and Rai stage. Results: Among the 1,090 CLL/MBL individuals, 833 (76%) had CLL. The median age at diagnosis was 64 years (range 24-89), with 65% being men, and 230 (21%) reported a prior history of NHM. The most common tumor was non-melanoma skin cancer (NMSC, 8.9%, 96 individuals), followed by prostate, testicular, and penile tumors (7.3%, 51 individuals), and melanoma (1.9%, 20 individuals). CLL/MBL patients with a prior history of a NHM were more likely to be over 65 years old (29%) than under 65 years old (14%, p < 0.0001). After a median follow-up of 2.9 years (range 0-21), 470 CLL/MBL patients progressed, requiring CLL treatment. CLL/MBL individuals with a prior history of NHM had a longer TTFT compared to those without (HR=0.69; 95% CI: 0.53-0.90; p=0.006). Individuals with a prior history of NHM who had either intermediate or high-very high CLL-IPI score had significantly longer TTFT (HR= 0.55; 95% CI: 0.33-0.92; p=0.02, and HR=0.65; 95% CI: 0.43-0.97; p=0.03, respectively) compared to those without NHM. After a median follow-up of 8.6 years (range 0-21), 359 individuals died. CLL/MBL patients with a prior history of NHM also experienced reduced OS compared to those without (HR=1.46; 95% CI: 1.08-1.97, p=0.013), particularly among those with low (HR=1.70; 95% CI: 0.96-3.00, p=0.07) or intermediate-risk (HR=2.08; 95% CI: 1.24-3.51, p=0.006), according to CLL-IPI. After excluding NMSC, results remained constant. Conclusions: At the time of diagnosis, one out of five CLL/MBL individuals had a prior history of a NHM. These individuals had a longer time to first CLL directed treatment and reduced OS, even after accounting for other important CLL prognostic factors, which deserves additional studies. Citation Format: Bryan A. Vallejo, Cristine Allmer, Kari G. Rabe, Dennis P. Robinson, Yucai Wang, Paul J. Hampel, Esteban D. Braggio, Neil E. Kay, James R. Cerhan, Sameer A. Parikh, Susan L. Slager. The impact of prior history of non-hematologic malignancies on time to first treatment and overall survival among individuals with CLL or MBL [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 7450.

Abstract Introduction: Laparoscopy with peritoneal lavage enhances staging accuracy in patients with pancreatic ductal adenocarcinoma (PDAC). Occult intra-abdominal metastases are identified by staging laparoscopy in approximately 20% of patients with radiologically localized PDAC. Peritoneal fluid cytology has limited sensitivity in detecting occult intra-abdominal metastasis. Methylated DNA markers (MDMs) can accurately detect PDAC from tumor tissue, blood, and pancreatic secretions. This study aims to assess the feasibility of assaying MDMs in peritoneal lavage fluid obtained at the time of staging laparoscopy for patients with PDAC. Methods: Peritoneal lavage fluid (25-60 mL) obtained from patients with PDAC at the time of staging laparoscopy was centrifuged for 10 minutes at 1200 × g. The pellet was resuspended and aliquoted into 200µL tubes and frozen at -80°C. DNA extracted from one aliquot was assayed for mutant KRAS (G12A and G13D) and then bisulfite converted to measure 13 MDMs (GRIN2D, CD1D, ZNF781, FER1L4, RYR2, CLEC11A, AK055957, LRRC4, MAX.CHR5.4295, HOXA1, PRKCB, SHISA9, NTRK3) and a normalizing reference gene (B3GALT6) using quantitative methylation specific PCR. The association of KRAS and the average signal from the 13 MDMs (MDMscore) with intra-abdominal metastasis (Y/N) was assessed with the area under the receiver operator characteristic curve (AUC). Results: Among 48 PDAC patients, staging laparoscopy revealed intra-abdominal metastasis in 15 (31%). Of the 15 intra-abdominal metastases, 6 were found to have biopsy-confirmed intra-abdominal metastasis and positive peritoneal cytology, 4 were positive on peritoneal cytology alone, and 5 had biopsy-confirmed intra-abdominal metastasis alone. The sensitivity of the MDMscore for intra-abdominal metastasis was 87% (CI: 60-98%) at 90% (CI: 76-98%) specificity whereas the sensitivity for KRAS was 40% (CI: 16-68%) at 85% (CI: 68-95) specificity. The AUC for the MDMscore was 0.98 (CI: 0.94-1.00) compared to 0.62 (CI: 0.48-0.77) for that of KRAS (p<0.0001). Conclusion: MDMs assayed from peritoneal lavage fluid collected during staging laparoscopy is a novel tool for accurate molecular staging of PDAC. These early results warrant further study in a larger cohort to assess impact on peritoneal staging and its clinical utility in the neoadjuvant treatment paradigm of PDAC. Citation Format: Kalika Maheshwari, Calise K. Berger, William R. Taylor, Douglas W. Mahoney, Kelli N. Burger, Adriana M. Delgado, Karen A. Doering, Heather M. Streich, Patrick H. Foote, Sean P. Cleary, Travis E. Grotz, Micheal L. Kendrick, Rory L. Smoot, Patrick P. Starlinger, Cornelius A. Thiels, Mark J. Truty, Susanne G. Warner, John B. Kisiel, Shounak Majumder. Methylated DNA markers for detection of peritoneal metastasis in pancreatic cancer [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 3784.

Abstract Despite the current binary clinical classification of variants (pathogenic versus benign), it is widely recognized that risk is a continuum. Prior studies have suggested the existence of reduced penetrance pathogenic variants (RPPVs), which pose challenges for identification, reporting, patient counseling and care. Through the current study, we sought to establish RPPVs as a new category of variants, with efforts focused specifically on BRCA1 and BRCA2 (BRCA). We compiled, compared, and assessed data for BRCA RPPVs from two large clinical diagnostic laboratories to establish an initial set of reduced penetrance pathogenic variants. Specifically, candidate BRCA RPPVs provided by clinical diagnostic laboratories were compiled to identify those with the highest prior likelihood of being a RPPV, based on concordant interpretations. Evidence of reduced penetrance included: 1) the identification of biallelic Fanconi Anemia-affected carriers; 2) splicing, missense, and nonsense-mediated RNA decay (NMD)-escaping variants; 3) laboratory-validated cancer history weighting models; 4) published variant-specific risk estimation data; 5) extrapolation of a reduced-risk interpretation onto close match variants that are expected to have the same effect; and 6) functional data. Sixteen candidate BRCA RPPV present in both lists from both laboratories were systematically assessed. For BRCA1, variants included c.5096G>A p.(Arg1699Gln) and variants impacting the canonical c.671 splice acceptor site. For BRCA2, variants included three frameshift (c.658_658delGT, c.9672dupA, c.9699_9702delTATG), two spliceogenic (c.8488-1G>A and c.8488-1G>T), and three missense (c.7878G>C, T, p.(Trp2626Cys); and c.9302T>G p.(Leu3101Arg)) variants. Our study is the first to clearly evaluate and establish BRCA RPPVs as a new class of variants, based on consistency in results across 16 variants using different interpretation strategies between laboratories. These variants impart a moderately increased risk of breast cancer, often considered to be between 2-4 fold, which should be considered when determining risk-informed cancer prevention strategies. Furthermore, our study establishes a framework to harmonize interpretation and standardize reporting of BRCA RPPV, by providing evidence to support this new classification for 16 variants. Further work to define clinically meaningful risk thresholds and categories for reporting BRCA RPPV are needed to personalize cancer risks in conjunction with other risk factors. Citation Format: Tuya Pal, Erin Mundt, Marcy Richardson, Elizabeth Chao, Tina Pesaran, Thomas P. Slavin, Fergus Couch, Alvaro N. Monteiro. Reduced penetrance BRCA1 and BRCA2 pathogenic variants in clinical germline genetic testing [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 6615.

Abstract Background: Although targeting myeloid cells has become one of the next generation targets for cancer immunotherapy, there is a lack of therapeutic tools to specifically target these cells. Our group has developed a novel humanized PD-L1-targeting antibody, H1A, that induces PD-L1 degradation via blockade of PD-L1 and CMTM6, therefore limiting PD-L1 intrinsic signaling while also preventing interactions with PD-1. In the immune cell compartment, CMTM6 expression is restricted to myeloid cells, making these cells the primary target of H1A. Recently, we unexpectedly found that targeting intrinsic PD-L1 in myeloid cells via H1A resulted in increased release of CCL2 from myeloid cells. In this study, we examined the role of CCL2/CCR2 signaling in CD8 T cell function using human peripheral blood-derived immune cells and evaluated the therapeutic potential of H1A antibody using our humanized PD-L1/PD-1 mouse model. Methods: Human PBMCs derived from healthy donors were treated with H1A or Atezolizumab, a blocking PD-L1 antibody, followed by mass cytometry and flow cytometry to evaluate immune cell phenotype and functional states. PD-L1 expressing myeloid cells isolated from human PBMCs were treated with H1A or Atezolizumab and assessed for CCL2 secretion using multiplex immunoassays. CCL2 production and transcription were confirmed by flow cytometry and single-cell RNA-sequencing. CCR2 blockade was used on human PBMCs to evaluate the effects of CCL2/CCR2 signaling on T cell function alongside H1A treatment. Finally, in vivo antitumor activity of H1A and Atezolizumab were compared in two humanized PD-L1 tumor models. Results: H1A reduced the frequency of regulatory T cells and increased effector T cells, in whole PBMCs upon global T cell activation with anti-CD3/CD28. H1A enhanced the secretion and production of CCL2 from myeloid cells, which was confirmed at a transcript level. CCR2 blockade diminished CD8 T cells’ ability to differentiate into effector cells in H1A treated PBMCs. H1A demonstrated comparable therapeutic effects with Atezolizumab in treatment of immunogenic and ICI-responsive mouse tumor MC38, which is CD8 T cell-dependent, but showed superior therapeutic effects in treatment of ICI-insensitive mouse tumor E0771 compared to Atezolizumab. Both treatments elicited durable memory specific immune responses upon E0771 tumor rechallenge. Conclusion: H1A demonstrated a superior antitumor activity compared to Atezolizumab in our preclinical models via a new mechanism by which H1A caused degradation of intrinsic PD-L1 in myeloid cells. This causes more release of CCL2 to improve T cell function via CCR2 upon T cell activation. Thus, H1A is emerging as a new immunotherapy tool to target PD-L1/CMTM6 in myeloid cells for treatment of cancers that are refractory to current immune checkpoint inhibitor therapy. Citation Format: Michelle Alexandria Hsu, Xin Liu, Ying Li, Whitney Barham, Kevin Pavelko, Jake Hirdler, Fabrice Lucien, Haidong Dong. Targeting PD-L1/CMTM6 in myeloid cells results in elevated release of CCL2 to improve CD8 T cell-mediated antitumor response [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 2664.

Abstract Breast cancer rates among women younger than 50 years-old have been steadily increasing since the mid-1990s. There is consistent evidence that use of combination estrogen and progesterone oral contraceptives (OCs)—including contemporary formulations with lower estrogen—increases breast cancer risk. It is unclear, however, if this risk varies by factors such as progestin type in the OC formulation, timing of OC use, histopathologic characteristics of the breast cancer, or individual patient characteristics. This study included premenopausal women aged <50 years and cancer-free when they enrolled in the U.S.-based American Cancer Society Cancer Prevention Study-3 cohort between 2006 and 2013 (n=101,838 women). At enrollment participants responded to a detailed life history questionnaire including questions about type, brand, duration, and recency of OC use. Incident breast cancers diagnosed between 2006-2018 were identified through cancer registry linkages (n=759). Participants were followed until the first of 1) breast cancer diagnosis, 2) age >50 years, or 3) December 31, 2018. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate associations between OC use and breast cancer risk. On average, participants were 39.3 years at baseline and were followed for 5.7 years (up to 12.3 years). Current versus never use of OCs for 10+ years was associated with a higher risk of breast cancer (10-<20 years: HR=1.46, 95% CI: 1.03-2.07; 20-<30 years: HR=1.66, 95% CI: 1.14-2.41; 30+ years HR= 2.51, 95% CI: 0.77-8.16). Cessation of OC use progressively attenuated the association down to the null 15 years after discontinuation of use (HR=1.04, 95% CI: 0.73-1.49). Associations with current OC use varied by generation of progestin in the formulation (first generation: HR=1.37, 95% CI: 0.93-2.02; second: HR=1.79, 95% CI: 1.20-2.67; third: HR=1.65, 95% CI: 1.13-2.42; fourth: HR= 0.91, 95% CI: 0.49-1.67). The strongest associations were observed for use of formulations with norgestrel: HR=2.82, 95% CI: 1.54-5.19; norgestimate: HR=1.80, 95% CI: 1.19-2.72; and levonorgestrel: HR=1.56, 95% CI: 1.00-2.43. The OC-breast cancer associations were primarily limited to localized, grade 1 or 2, and ER+ disease. Race, income, body mass index, physical activity, alcohol use, cigarette smoking, parity, and breastfeeding did not appear to modify the associations. There were also no clear differences in the associations based on age at first or last OC use or timing relative to pregnancy. Current, long-term OC use was associated with increased risk of early-onset breast cancer. These data suggest that risks may vary with progestin content, and future studies are needed to define formulations that minimize breast cancer risk while still maximizing protection against other female cancers. Citation Format: Lauren R. Teras, Emily L. Deubler, Mark E. Sherman, Clara Bodelon, Lauren E. McCullough, James M. Hodge, Sicha Chantaprasopsuk, Alpa V. Patel. Factors modifying the association between hormonal contraception and risk of early-onset breast cancer [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 3442.

Abstract The Voyage Study is a large-scale, prospective cohort study of long-term health outcomes among participants with a valid multi-target stool DNA (mt-sDNA) test order. Recently, the Voyage Study achieved its enrollment target of 150,000 participants. The intent of this descriptive analysis is to provide baseline geographic and socio-demographic characteristics of Voyage Study participants to set the stage for future comparisons to the broader mt-sDNA user population. Participants were randomly selected from all persons in the U.S. or Puerto Rico who had a valid order for mt-sDNA screening during the enrollment period (10/18/2019 - 10/17/2023). Enrolled participants completed a baseline questionnaire that collected socio-demographic and health information. Participant characteristics and baseline survey answers were compared between regions using chi-square tests where appropriate. Regional geographic data was aggregated for the broader mt-sDNA user population during the enrollment period, though no formal comparisons were made between the broader population and the Voyage population at this time. Analyses were limited to 139,369 participants with available baseline questionnaire data. Voyage participants were more likely to reside in the Midwest, Northeast, or Southeast (29.9%, 22.5%, 22.6% respectively) and less likely to reside in the Southwest and West (11.6%, 13.4%). During the enrollment period, differential participation was also observed in the mt-sDNA user population, with the Midwest, Northeast, and Southeast having the greatest proportion (25.4%, 22.2%, 26.7%) and the Southwest and West having the lowest proportion of mt-sDNA users (13.8%, 11.9%). In the Voyage cohort, Midwest participants reported the lowest education attainment as characterized by years of school completed (14.1% high school or below, 59.2% college or greater), while participants in the West reported the highest education attainment (7.9% high school or below, 67.3% college or greater). The West also had the highest percentage of participants reporting an income of $100,000 or greater (51.6%), with the Southeast being the lowest (42.2%), as compared to the other regions. We report here early results of geographic and socio-demographic characteristics from a new research resource that will enable future analyses of health outcomes and behaviors in a population of mt-sDNA users. We observed that the greatest percentage of Voyage participants resided in the Midwest, Northeast, or Southeast, and that there was differential socio-demographic participant characteristics based on region. Future analyses will compare long-term healthcare outcomes and differences in colorectal cancer incidence and mortality between the broader mt-sDNA user population and the Voyage cohort. Citation Format: Allison M. Berry, Jessica A. Grimm, Christine R. Kirt, Emily J. Kirsch, Rachel E. Dixon, Winnie Z. Fan, Kandace A. Bohn, Jennifer St. Sauver, Kathleen J. Yost, Lila J. Finney Rutten, Janet E. Olson. U.S. Geographic and socio-demographic characteristics of Voyage Study participants [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 3453.