University of Florida Health Science Center

Aim To examine the relationship between social determinants of health (SDOH) challenges and perceptions of climate change harm among US adults using nationally representative data. Subject and methods Analysis of the 2022 Health Information National Trends Survey (HINTS 6) data from 5888 US adults. The study assessed three key SDOH challenges experienced in the previous 12 months: food insecurity, housing instability, and transportation insufficiency. The primary outcome measure was self-reported perception of climate change’s potential harm to personal health, measured on an ordinal scale from “Don’t know/Not at all” to “A lot.” Multivariate analyses were conducted to examine associations between SDOH challenges and climate change harm perceptions. Results Individuals frequently experiencing food insecurity showed significantly higher odds of perceiving greater climate change-related health risks (OR 2.31, 95% CI 1.28–4.20) compared to those never reporting such challenges. Similarly, frequent housing insecurity was associated with increased odds of perceived harm (OR 2.30, 95% CI 1.12–4.74). A dose–response relationship was observed, with each 6-point increase in cumulative SDOH challenge score corresponding to more than threefold higher odds of perceiving greater climate change harm (OR 3.19, 95% CI 1.67–6.08). These associations remained significant after adjusting for demographic and socioeconomic factors. Conclusion SDOH challenges significantly influence climate change risk perception among US adults. These findings suggest the need for integrated intervention strategies that address both social vulnerabilities and climate resilience, particularly among populations experiencing concurrent SDOH challenges.

Purpose Pancreatic acinar cell carcinoma accounts for 1–2% of pancreatic tumors, with increasing frequency in recent years, and still represents a poor prognosis. This study aims to expand and update existing literature by analyzing national data gathered over almost two decades. Methods Data from 488 patients diagnosed with PACC in the Surveillance, Epidemiology, and End Results database were analyzed. This study employed the Cox regression method to compute hazard ratios and identify independent factors influencing survival. Additionally, Kaplan–Meier survival curves were utilized alongside the log-rank test. Results The median age was 64.7 years with male predilection (70.5%). “Poorly differentiated carcinoma” was the most common subtype (45.8%). The liver was the most common site of metastases (31.3%). The 5-year observed overall survival (OS) rate was 19.2% (95% CI, 14.9–23.8). The 5-year cause-specific survival (CSS) rate was 22.4% (95% CI, 17.7–27.5). Male gender has a 5-year OS of 19.2% (95% CI, 14.0–25.1) compared to female OS of 30.2% (95% CI, 20.7–40.1). Patients treated with multimodal therapy (surgery with chemoradiation) over only surgery or chemotherapy had better 5-year OS, 53.5% (95% CI, 31.8–71.0). Age > 60 and distant stage were independent factors associated with increased mortality. Conclusion Pancreatic acinar cell carcinoma is a rare, aggressive form of pancreatic cancer that primarily affects older adults. Our findings offer valuable insights to guide future clinical guidelines and tailored treatment strategies.

The healthcare community has, in recent years, paid increased attention to errors in the diagnostic process, especially in emergency departments (EDs). However, the expertise of frontline professionals could be an important factor in mitigating risks, preventing diagnostic errors, and improving performance. The current research focused on identifying expertise in ED personnel, complementing efforts to examine errors in reasoning or diagnosis. Data were collected from a three-year, multi-site examination of various EDs. Through the analysis of 43 Critical Decision Method interviews (Klein, Calderwood, & MacGregor, 1989), we identified six aspects of ED expertise: technical, perceptual, organizational, teamwork, emotional, and sensemaking. We also identified barriers to the development of expertise in the ED, such as limited follow-up and feedback on cases. Our findings were consistent with other naturalistic examinations of expertise. Finally, we discuss implications for ED practice, diagnostic safety, and training.

Background and objectives: Disturbances in brain catecholamine activity may be associated with symptoms after exposure to repetitive head impacts (RHIs) or related chronic traumatic encephalopathy (CTE). In this article, we studied CSF catecholamines in former professional and college American football players and examined the relationship with football proxies of RHI exposure, CTE probability, cognitive performance, neuropsychiatric symptoms, and parkinsonism. Methods: In this observational cross-sectional study, we examined male former American football players, professional ("PRO") or college ("COL") level, and asymptomatic unexposed male ("UE") individuals from the DIAGNOSE CTE Research Project. Catecholamines-norepinephrine (NE) and its metabolite, 3,4-dihydroxyphenylglycol (DHPG), and dopamine (DA) and its precursor, 3,4-dihydroxyphenylalanine (l-DOPA), and metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC)-were measured in CSF with high-performance liquid chromatography and compared across groups with analysis of covariance. Multivariable linear regression models tested the relationship between CSF catecholamines and proxies of RHI exposure (e.g., total years of playing American football), factor scores for cognition, and neurobehavioral dysregulation (explosivity, emotional dyscontrol, impulsivity, affective lability), as well as depressive/anxiety symptoms, measured with the Beck Depression/Anxiety Inventories. CTE probability and parkinsonism were assessed using the National Institute of Neurological Disorders and Stroke consensus diagnostic criteria for traumatic encephalopathy syndrome (TES), and biomarkers were compared among different diagnostic groups. Results: The cohort consisted of 120 former American football players (85 PRO players, 35 COL players) and 35 UE participants (age 45-75). Former players had significantly lower levels of NE (mean difference = -0.114, 95% CI -0.190 to -0.038), l-DOPA (-0.121, 95% CI -0.109 to -0.027), and DOPAC (-0.116, 95% CI -0.177 to -0.054) than UE participants. For NE and DOPAC, these overall group differences were primarily due to differences between the PRO and UE cohorts. No significant differences were found across TES-CTE probability subgroups or TES-parkinsonism diagnostic groups. Within the COL cohort, tested as post hoc analyses, higher CSF NE and l-DOPA were associated with higher neurobehavioral dysregulation factor scores, BAI total score, and worse executive functioning and processing speed. CSF DHPG and DOPAC were associated with impulsivity only in this subgroup. Discussion: We observed reduced CSF catecholamine concentrations in former elite American football players, although the relationship with degree of RHI exposure and the clinical impact needs further study.

Introduction With the reduction in human immunodeficiency virus (HIV)–related mortality secondary to antiretroviral therapy, chronic medical conditions and age‐related cancers account for a larger proportion of mortality among those with HIV. Cancer risk overall remains elevated in HIV patients, and cancer screening data in this population is limited. The primary study aim was to determine whether screening colonoscopy findings differed between HIV and non‐HIV patients. Methods A retrospective review of adults with/without HIV undergoing screening colonoscopy between February 2015 and September 2022 was performed. HIV patients were matched with non‐HIV patients by sex, race, and age, undergoing screening colonoscopy within six business days of their matched patients. Demographic data included age, race, sex, family history of colorectal cancer (CRC), smoking status, alcohol use, along with endoscopic and histologic findings that were compared between the matched pairs. Results Ninety matched pairs of HIV and non‐HIV patients undergoing screening colonoscopy comprised the study population. The study group was 78.9% African American, 55.6% male, with a mean age of 59.0 years in HIV patients and 54.9 years in non‐HIV patients. Procedure indication was average risk screening in 91.1% of patients. No statistically significant differences in screening colonoscopy findings or polyp histology were observed between HIV and non‐HIV patients. Discussion Similar rates of polyps were found at screening colonoscopy regardless of HIV status. CRC screening recommendations are appropriate for the HIV patient population without limitation.

Patients with burn injuries comprise a unique population requiring specialty care. Burn teams are equipped to care for burn injuries from admission to discharge. The pharmacist clinician is a member of the burn team and can contribute to optimizing positive outcomes for these patients. This chapter is presented as a review of the unique aspects of burn care with which the pharmacist clinician will encounter and should be familiar. Classification of the depths of burns, typical surgical treatment, wound infections and topical agents, resuscitation, inhalation injury, antimicrobial dosing, hypermetabolism, pain and analgesia, micronutrients, and venous thromboembolism prophylaxis are reviewed and discussed.

Background The dose‐averaged linear energy transfer (LETD) in proton therapy (PT) has in pre‐clinical studies been linked to the relative biological effectiveness (RBE) of protons. Until recently, the most common PT delivery method in prostate cancer has been double‐scattered PT, with LETD only available through dedicated Monte Carlo (MC) simulations. However, as most studies of the relationship between LETD and RBE in double scattered PT have been focused on the head and neck region, existing MC implementations have not been capable of calculating LETD for the longer field ranges used, for example, in the pelvic region. Purpose The initial aim of this study was to implement a MC code allowing for LETD calculations in double‐scattered PT of prostate cancer. Additionally, we explored LETD profiles and LETD as a function of field configuration, by performing MC calculations for a large prostate cancer cohort treated with double‐scattered PT. Methods The components of a passive scattered clinical treatment nozzle used for delivery of extended field ranges, with two associated modulation wheels, were implemented into an existing FLUKA MC framework for LETD calculations. The code was validated to spread out Bragg peak (SOBP) measurements conducted using the treatment nozzle with 11 different range and modulation width configurations. After validation, LETD distributions were calculated on the planning computed tomographies of 582 prostate cancer patients treated with two‐field double‐scattered PT. All patients had symmetric field configurations with respect to the sagittal plane, with one pair of posterior oblique, lateral opposing, or anterior oblique fields. Dose and LETD volume parameters and the mean LETD ratio between the bladder and rectum were compared across the three groups. Results The range differences were below 1 mm for all SOBP scenarios used for calibration. For 9 of 11 SOBP scenarios, the modulation width differences were below 2 mm. For the patient simulations, the mean gamma pass rates (3 mm/3%) were at least 98% in the PTV, bladder, and rectum. Comparing anterior to posterior field configurations, the mean LETD in the bladder increased within both the 10 and 70 Gy iso‐dose regions, and conversely, the mean LETD decreased for the rectum. There was a marked difference in the mean bladder‐to‐rectum LETD ratios between anterior oblique, lateral opposing and posterior oblique field configurations. Conclusion A MC code allowing for accurate calculations of dose and LETD in double‐scattered PT of prostate cancer was implemented and validated. The LETD distributions in the rectum and bladder showed a systematic dependence on the field configuration.

Older adults’ (adults over age 50) preferences for educational programs on integrative pain management have not been adequately explored. Integrative pain management uses a holistic approach combining traditional medical treatments with alternative non-pharmacological practices. Pain-related education targeting older adults is supported by prior research, but to our knowledge older adult perspectives and learning preferences have not been investigated. Our objective was to explore older adult views on integrative pain management, specifically their educational needs and preferences, for patient-centered pain management education. Patients >50 years of age with chronic pain (pain for three months or longer), were eligible for enrollment in virtual focus groups. Audio recordings were transcribed, coded, and analyzed via a mixed inductive-deductive framework approach using ATLAS.ti version 23.0.8.0 (Microsoft, Redmond, WA, USA). Descriptive statistics were performed using Stata 16 (StataCorp., College Station, TX, USA). There were 16 participants and five themes generated: opioid/analgesic perceptions, integrative pain management, patient-provider relationship, and educational needs/preferences. All participants felt traditional interactions with healthcare providers did not adequately address their educational needs. There were discordant views on opioids, some noted positive impacts on pain and function and others feared addiction and side effects. Subthemes on the patient-provider relationship were identified including misalignment in treatment preferences/goals and communication gaps. Participants preferred virtual programs, incorporating demonstrations, audience interaction, and physical materials. These findings can be used to develop patient-centered educational programs

PURPOSE Circulating tumor DNA (ctDNA) is an emerging tool in the evaluation of GI cancers. Challenges remain in defining its utility and role as a primary end point in therapeutic trials. The National Cancer Institute (NCI) ctDNA GI working group was created to evaluate current data and provide guidance on the inclusion of ctDNA in GI cancer trials. METHODS The NCI GI steering committee assigned four task force members to serve as co-chairs for the working group. Co-chairs identified experts within each GI disease group to form a panel that convened to review data and provide recommendations. The group focused on ctDNA's role as a potential surrogate for assessing prognosis and guiding treatment decisions that may enhance GI cancer trials. A manuscript was drafted, circulated, revised, and voted on by the panel. The final draft was reviewed by the Cancer Therapy Evaluation Program. RESULTS Further data are required to support ctDNA as a primary end point for late-phase therapeutic trials, particularly in studies that could change the standard-of-care. However, the group supports ctDNA as a primary efficacy end point for phase II studies and as a noninvasive evaluation strategy for new drug development. Incorporation of ctDNA as a biomarker in trial design must consider the specific context of disease biology of the GI cancer subtypes. ctDNA should be incorporated as an exploratory end point across a variety of disease settings and indications. Several practical considerations were identified to optimize the incorporation of ctDNA in future trial design. CONCLUSION Prospective trials are required to clarify the role of ctDNA as a valid surrogate end point for progression-free or overall survival in GI cancers.

Cancer cachexia is the involuntary loss of body and skeletal muscle mass, which negatively impacts physical function, quality of life, treatment tolerance, and survival. Skeletal muscles of cachectic people and mice with pancreatic tumors also exhibit skeletal muscle damage, non-resolute immune cell infiltration, and impaired regeneration. These phenotypes may be influenced by the accumulation of senescent cells, which secrete factors detrimental to skeletal muscle health. However, there is currently no comprehensive research on senescent cell accumulation in skeletal muscle of tumor-bearing hosts, with or without chemotherapy. To address this gap, we cross-referenced the SenMayo panel of 125 senescence-related genes with our RNA-seq dataset in mouse skeletal muscle during the initiation and progression of cancer cachexia, which revealed a differential expression of 39 genes at pre-cachexia, 64 genes at cachexia onset, and 72 genes when cachexia is severe. Since p16 is a canonical marker of senescence, we subsequently orthotopically injected p16-tdTomato reporter mice with murine KPC pancreatic cancer cells and treated a subset of mice with chemotherapy. At experimental endpoint, when KPC treatment-naïve mice were cachectic, we observed an increased accumulation of p16+ cells, along with increased mRNA levels of hallmark senescence markers ( Cdkn1a/p21, Cdkn2a/p16, Glb1/senescent-associated-β-galactosidase), which were exacerbated by chemotherapy. Lastly, we demonstrate an increase in CDKN1A/p21 in the muscle of cachectic patients with pancreatic cancer, which associated with cachexia severity. These findings suggest that senescent cells accumulate in skeletal muscle of cachectic pancreatic tumor-bearing hosts and that chemotherapy can exacerbate this accumulation.

Transcatheter aortic valve implantation (TAVI) has significantly improved in treating aortic valve disease in recent years, particularly in patients at high surgical risk. This case report describes an 80-year-old woman who had severe aortic stenosis previously treated with surgical aortic valve replacement (SAVR) and six years later had a valve-in-valve (ViV) TAVI who developed severe symptomatic restenosis of the bioprosthetic aortic valve five years later of the last procedure. A third valve-in-valve-in-valve (ViViV) TAVI using a 26-mm Sapien 3 valve was performed due to the high surgical risk. The procedure resulted in significant hemodynamic improvement, reducing the transvalvular gradient from 80-90 mmHg to 15-20 mmHg and increasing the effective orifice area from 0.4 cm² to 1.5 cm². The patient’s symptoms improved to NYHA Class I. This case highlights the feasibility and safety of ViViV TAVI as a minimally invasive solution for recurrent bioprosthetic valve dysfunction in high-risk patients.

Background Septic pulmonary embolism (SPE), resulting from infections such as osteomyelitis and endocarditis, is rare and lacks specific diagnostic guidelines. This report reviews the clinical manifestations, radiographic abnormalities and antibiotic therapy in children with SPE. Methods Patients aged 1 to 18 years with confirmed SPE were identified from a database using the International Classification of Diseases-9/10 codes from 2000 to 2020. After excluding duplicates and those with neoplastic disease, 8 patients were included out of 16 encounters. Results Patients predominantly presented with shortness of breath, fever and chest pain. Half had identifiable extrapulmonary infection sources. Leukocytosis was present in 50% and leukopenia in 12.5%. Anemia was noted in 87.5% of patients, possibly linked to patients’ acute illness. Contrasted chest computed tomography showed bilateral emboli in most patients. Echocardiograms were normal. Methicillin-resistant Staphylococcus aureus was identified in 62.5% of cases and oxacillin-sensitive staphylococcus aureus in 37.5%. While osteomyelitis was the most common infection source, our series uniquely included cavernous sinus thrombosis in children and reported for the first time. Most patients were empirically treated with vancomycin. Conclusion This case series highlights cavernous sinus thrombosis as a new clinical entity associated with pediatric SPE. It emphasizes the significance of prompt, targeted antibiotic therapy for improved outcomes in children with SPE.

TPS325 Background: Colorectal cancer (CRC), the second leading cause of cancer deaths in the US, is increasingly diagnosed in individuals under 50. This rise in early-onset CRC (eoCRC) led the U.S. Preventative Services Task Force to recommend a reduction in the age to begin colorectal cancer screening in average-risk persons, from 50 to 45. The etiology of eoCRC is multifaceted, with one postulated theory pointing to alterations in the young adult colonic microbiome. Hydrogen sulfide (H 2 S) producing bacteria, like Bilophila wadsworthia , Fusobacterium nucleatum and Atopobium parvulum , are typically minor gut microbiota components but are overrepresented in CRC cases, linked to inflammation, and may promote a pro-carcinogenic environment. These bacteria preferentially use taurine, an essential amino acid, as a primary energy source. Energy drinks represent one of the largest dietary sources (6-16x normal daily intake) of taurine in contemporary diets. Our hypothesis is that high taurine levels in energy drinks could exacerbate CRC risk by promoting preferential growth and metabolic activities of already present H 2 S-producing bacteria, contributing to the rise of eoCRC. Methods: This randomized open-label trial is actively enrolling up to 60 young adults (18-40 years) without personal or family history of CRC, other major GI disease/distress, and baseline infrequent energy drink consumption. Group 1 (Arm A; n=30), will consist of subjects consuming at least one of two protocol-specified energy drinks daily for 4 weeks. Group 2 (Arm B; n=30), will consist of usual dietary intake. Enrollments are randomized 1:1 and stratified, by gender, age (18-25 vs. 26-40), and baseline energy drink consumption (rare/none vs. 1-2 per week). Every subject will complete: 1) a daily dietary and fitness log, 2) a weekly wellness log, 3) collection of stool/saliva/skin/urine at 3 sequential time points (baseline, after 2 weeks, after 4 weeks), and 4) blood collection at the same time points. The primary endpoint is the change in H 2 S-metabolizing bacterial communities between baseline and 1 month of energy drink exposure within Arm A and also compared to those in Arm B using microbiome analysis (diversity, taxonomy, sulfur-enriched gene pathways). Several secondary and exploratory assessments include changes related to subject demographic and dietary differences, concordance of microbiome changes with dietary logs and in other biospecimens beyond stool, H 2 S-production measurements, and analyses of subject metabolic and immune function. Trial opened in February 2024 with active enrollment ongoing. Updated data on trial status and any amendment modifications will be presented at the meeting. Clinical trial information: NCT06137248 .

839 Background: Circulating tumor DNA (ctDNA) is a promising tool for monitoring treatment response but is challenged by pan-cancer quantification and consistent outcome correlations. Northstar Response (NSR) quantifies >500 cancer specific methylated loci, offering a reflection of disease burden and clinical response. Methods: We present a prospective observational study to evaluate the clinical utility of NSR. Patients with advanced GI cancers had serial ctDNA assessed at baseline and during systemic treatment with correlations to radiographic or clinical response. Tumor methylation scores (TMS) were expressed as Log10 values and a mixed-effects model evaluated clinical assessment correlations. Results: 73 patients with locally advanced or metastatic GI cancers were analyzed. Among these, 35 (47.9%) had at least four ctDNA assays and all had radiographic or clinical response assessments. The median age was 66 years (± 8.5), with most being male (67.1%) and White (74.0%). Table 1 shows the case distribution. Baseline TMS had significant variation (p=0.023), but was measurable across all tumor types. CRC exhibited the highest mean TMS-log10 while biliary and pancreatic cancers had the lowest. Cases with both primary and metastatic lesions had a higher mean TMS-log10 than cases with either primary tumors alone or metastatic lesions alone (3.4 vs. 3.0). Compared to stable and responsive disease, TMS changes correlated with progressive disease, with a coefficient of 0.48 at the third collection time point (p=0.05). However, 23/73 (32%) cases were without an on-treatment TMS timepoint (OTT) due to rapid progression (average time to death of 24 vs. 103 days for patients with OTT). In exploratory modeling of TMS relative to RECIST-like treatment response for those with OTT, NSR evaluations were associated with response assessments (p<0.04, Fisher’s Exact Test). Conclusions: TMS was consistently measurable but varied across tumor types and correlated with disease burden. TMS changes appeared associated with response assessments when accounting for rapid progressors. Additional analyses are ongoing and will be presented. Baseline study cohort characteristics. Characteristic HCCN = 25 (34%) BTC N = 12 (16%) EGAN = 12 (16%) CRCN = 11 (15%) PDACN = 8 (11%) Other GI N = 5 (7%) p-value Age Median (25% to 75%) 67 (63 - 76) 68.5 (62.3 – 75.5) 73.5 (62.5 – 75.3) 54 (39.5 – 60) 67.5 (55.5 – 76.3) 60 (57 – 63) 0.008 Baseline TMS Log10 Median (25% - 75%) 3.2 (2.3 – 3.9) 2.5 (2.1 – 3.4) 3.2 (2.2 – 3.8) 4.4 (3.5 – 5) 2.5 (1.9 – 3.3) 4 (3.4 – 5.2) 0.023 Primary tumor present 12 (48%) 8 (66.7%) 12 (100%) 6 (54.5%) 7 (87.5%) 4 (80%) 0.015 First line therapy vs. not 23 (92%) 5 (41.7%) 5 (41.7%) 6 (54.5%) 3 (37.5%) 5 (100%) 0.001 Progressive disease 16 (64%) 4 (33.3%) 9 (75%) 5 (45.5%) 3 (37.5%) 4 (80%) 0.2 Death 13 (52%) 3 (25%) 9 (75%) 7 (63.6%) 3 (37.5%) 2 (40%) 0.2 Kruskal-Wallis rank sum test; Fisher’s exact test.

TPS309 Background: Patients with oligometastatic colorectal cancer (CRC) often experience long-term progression-free survival and overall survival (OS) following aggressive local treatment of isolated metastases, especially in the liver. However, the effectiveness of local ablative therapies, such as microwave ablation (MWA) and stereotactic body radiation therapy (SBRT), in patients with inoperable limited metastatic CRC or those with additional metastases outside the liver or lungs, remains uncertain. Despite the historical use of local therapy for oligometastatic CRC, often influenced by provider bias rather than strong evidence, questions persist about the potential benefits of applying this approach to patients with more extensive disease. This trial aims to address this clinical challenge by evaluating the safety and efficacy of adding total ablative therapy (TAT) of all disease sites to standard systemic treatment in patients with limited metastatic CRC. Methods: A022101/NRG-GI009 is a randomized phase III study within the National Clinical Trials Network, set to enroll 364 patients with newly diagnosed metastatic CRC (BRAF wild-type, microsatellite stable). Patients with liver-only metastatic disease are excluded. Pre-registration during first-line systemic therapy induction is encouraged. Eligible lesions must be treatable with surgical resection, MWA, and/or SBRT. Patients without significant radiographic progression after 12-39 weeks of first-line systemic therapy, with 4 or fewer disease sites post-induction chemotherapy, will be randomized 1:1. Randomization will be stratified by the number of metastatic organ sites (1-2 vs. 3-4), timing of metastatic disease diagnosis (de novo vs. secondary), and the presence of metastatic disease outside the liver/lungs in at least one site. Patients in Arm 1 will receive TAT, targeting all metastatic sites with a combination of surgical resection, MWA, and/or SBRT, followed by standard systemic therapy. Patients in Arm 2 will continue with standard systemic therapy alone. The choice of systemic therapy is at the discretion of the medical oncologist and may include continued therapy, maintenance chemotherapy, or observation. The primary endpoint is OS, with secondary endpoints including event-free survival, treatment-related toxicities, and local recurrence. Exploratory biomarker analyses will also be conducted. The study requires 346 evaluable patients across the two arms to demonstrate an OS improvement with a hazard ratio of 0.7, providing 80% power with a one-sided alpha of 5%. The trial employs a group sequential design with two interim analyses (at 25% and 50% of events) to assess futility. The trial began in January 2023, and patient recruitment is ongoing. Clinical trial information: NCT05673148 .

TPS310 Background: Currently, there are no biomarkers validated prospectively in randomized studies for resected colon cancer (CC) to determine need for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. CC pts who do not have detectable ctDNA (ctDNA-) are at a much lower risk of recurrence and may be spared the toxicities associated with AC. Furthermore, for CC pts with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence, the optimal AC regimen has not been established. We hypothesize that for pts whose CC has been resected, ctDNA status may be used to risk-stratify for making decisions about AC. Methods: In this prospective phase II/III trial, up to 1,912 pts with resected stage IIB, IIC, and III CC will be enrolled. Based on the post-operative ctDNA status using personalized and tumor-informed assay (Signatera, bespoke assay), those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP)+oxaliplatin (Ox) for 3-6 mos per established guidelines v serial ctDNA monitoring. Patients who are ctDNA+ post-operatively, or with serial monitoring (Cohort B), will be randomized to FP+Ox v more intensive AC with addition of irinotecan (I) for 6 mos. One cycle of chemotherapy is allowed while awaiting ctDNA testing results for cohort assignment. The primary endpoints for Cohort A are time to ctDNA+ status (phase II) and disease-free survival (DFS) (phase III) in the immediate v delayed AC arms. The primary endpoint for Cohort B is DFS in the FP+Ox v FP+Ox+I arms for both phase II and phase III portions of the trial. Secondary endpoints include prevalence of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and the assessment of compliance to adjuvant therapy. Biospecimens including archival tumor tissue, as well as post-operative plus serial matched/normal blood samples, will be collected for exploratory correlative research. Active enrollment across the NCTN started in June 2022 with CCTG sites joining in August 2023. Current accrual (as of 9-20-2024): 500/1,912. Clinical trial information: NCT05174169 .