Extrapulmonary neuroendocrine carcinomas (EP-NECs) are a heterogeneous group of rare tumors with poor clinical outcomes. These patients have limited treatment options after progressing on first-line platinum-based chemotherapy. Although dual immune checkpoint inhibitors (ICIs) with anti-CTLA-4 and anti-PD-1 blockade have significantly improved outcomes for several solid tumors, they demonstrated modest activity for EP-NECs with 9–26% response rates and low survival rates. Preliminary data demonstrated that NP-101 (Nigella sativa formulation) enhances T-cell infiltration and is synergistic with dual ICPIs in NECs’ cellular models. This pilot study evaluated the tolerability and efficacy of NP-101 plus nivolumab and ipilimumab in patients with metastatic EP-NECs refractory to first-line platinum-based chemotherapy. This is a single-arm pilot study (NCTNCT05262556) in which patients with metastatic EP-NECs received NP-101 (oral capsules), 3,000 mg daily, plus ICPIs (intravenous nivolumab 3 mg/kg and ipilimumab 1 mg/kg) every 3 weeks for four cycles. Nonprogressors received NP-101 (3,000 mg daily), plus biweekly maintenance of nivolumab (240 mg), and then completed 24 weeks of treatment. Treatment-related adverse events (TR-AEs) were characterized according to CTCAE v4.03. The response rate was estimated according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The Kaplan–Meir method was used to estimate median PFS and OS. Twelve patients received ≥1 dose of NP-101 and nivolumab plus ipilimumab. There were no dose-limiting toxicities (DLTs). Grade 1/2 TR-AEs occurred in 100% (12/12) of patients. The most common G1/2 TR-AEs included the following: fatigue (75%), nausea (41.7%), pruritus (41.7%), muscle weakness (33.3%), vomiting (25%), rash (25%), and abdominal pain (25%). Eight patients (66%) experienced grade 3/4 TR-AEs, including rash (33.3%), nausea (16.7%), vomiting (16.7%), and transaminitis (16.7%). No treatment-related grade 5 toxicities or deaths were recorded. The objective response rate was 41.7% (2/12 (16%) complete response (CR) + 3/12 (25%) partial response (PR); 95% CI: 15.2–72.3%) for all patients and 50% (2/8 CR + 2/8 PR, 95% CI: 0.16–0.84) for patients with NEC of gastrointestinal origin. The median duration of response was 7.5 months. As for the median progression-free survival, it was 5.7 months, and the median overall survival (OS) was 10.5 months with a median follow-up of 10.4 months. The combination of NP-101 plus dual ICPIs (nivolumab and ipilimumab) was safe and well tolerated with preliminary evidence of antineoplastic activity. Currently, a randomized phase II clinical trial evaluating the combination is under development.

INTRODUCTION:In this systematic review and associated guidelines, the American Radium SocietyTM (ARS) thoracic and gastrointestinal oncology expert panels worked together to thoroughly evaluate current literature and provide treatment recommendations for best outcomes for resectable esophagus or gastroesophageal junction adenocarcinoma. To represent a diverse group representing all key specialties, thoracic and gastrointestinal radiation and medical oncologists, gastroenterologists, and thoracic surgeons were included in development of these consensus guidelines. METHODS:Using the Population, Intervention, Comparator, Outcome, Timing and Study Design framework, the evidence was assessed using Cochrane and PRISMA 2020 methodology. Eligible studies included randomized Phase II and III trials and retrospective subset analyses of randomized controlled trials published between January 1, 2019 and July 7, 2025 in the Ovid Medline database. These references were assessed via ARS Appropriate Use Criteria (AUC) methodology. RAND-UCLA consensus methodology was used to rate the appropriateness of various treatments. RESULTS:For patients with adenocarcinoma of the esophagus or gastroesophageal junction, the standard treatment approach has been trimodality therapy including chemotherapy, radiation, and surgery which is associated with significant long-term toxicity. Recent randomized controlled trials have compared perioperative chemotherapy to trimodality therapy affording the omission of radiotherapy for suitable patients and a resulting reduction in associated treatment-related toxicities. Recommendations for adjuvant and neoadjuvant therapies are provided, including chemotherapy, immunotherapy, targeted therapy and radiation therapy, and active surveillance after chemoradiation is also detailed. CONCLUSIONS:The updated 2026 ARS AUC for Operable Esophageal and Gastroesophageal Junction Adenocarcinoma is presented in this manuscript.

Abstract Background EpCAM (Epithelial Cell Adhesion Molecule) is a cell surface protein overexpressed by most adenocarcinomas. BA3182, a novel dual-conditionally binding EpCAM x CD3 T cell engager (TCE), is designed to selectively bind to both EpCAM and CD3 in the acidic tumor microenvironment (TME). In healthy tissues, binding of BA3182 to both the EpCAM and CD3 receptors is greatly reduced or eliminated, thus avoiding on-target, off-tumor activity. Preclinical studies showed potent antitumor activity in colorectal and breast cancer models, with a > 100-fold improvement in therapeutic index over non-conditionally binding EpCAM x CD3 TCE's. Methods This phase 1 dose escalation study uses a Bayesian Optimal Interval design in treatment refractory adenocarcinoma patients. Patients received weekly intravenous (IV) or subcutaneous doses of BA3182. EpCAM expression in tumor specimens is characterized by immunohistochemistry. Results As of May 9, 2025, 30 pts were enrolled in cohorts ranging from 2.6-300 micrograms total dose of BA3182 administered weekly IV or subcutaneously. Tumor types include colorectal (n=l 7), PDAC (n = 4), breast (n = 2), cholangiocarcinoma (n = 2), esophageal (n=l), gallbladder (n=l), NSCLC (n=l), ovarian (n=l), and small bowel (n=l). Transient and manageable grade 1 (n = 2) and grade 2 (n=l) CRS were observed. Dose escalation continues at weekly subcutaneous doses of 300 micrograms and higher. Tumor reduction (CRC-8% and -10%; breast-11%; NSCLC-25%) has been observed prior to the 100 microgram dose level. Two pts with CRC experienced prolonged progression-free intervals (8 mo ongoing and 14 mo). Conclusions BA3182, a CAB-EpCAM x CAB-CD3 T-cell engager that selectively binds to both EpCAM and CD3 in the acidic TME, is associated with preliminary evidence of anti-tumor activity with acceptable tolerability in humans. Dose escalation continues.

OBJECTIVES:Rates of locoregional recurrence and distant metastases are high following curative-intent resection for patients with localized pancreatic adenocarcinoma. Adjuvant therapies have been investigated with the intent to reduce the risk of recurrence and improve OS. The objective of this study is to update and summarize the current evidence for adjuvant therapy following surgical resection for nonmetastatic PDAC with a focus on high-level evidence and randomized controlled trials is provided. METHODS:This multispecialty-led committee included gastrointestinal radiation and medical oncology, gastroenterology, radiology, and surgical oncology. Using the population, intervention, comparator, outcome, timing and study design framework, evidence regarding treatment outcomes was assessed using Cochrane and PRISMA methodology. Eligible studies included prospective and retrospective (n≥25) studies published between January 1, 2013 and February 13, 2026, from Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Review, and Scopus databases. Study type and quality were assessed. Well-established RAND/UCLA consensus methodology (modified Delphi) was used to rate the appropriateness of the treatment options. RESULTS:Of the 74 references used as evidence, 74 are categorized as therapeutic references. Study type and quality for the references were assessed, and included 31 well-designed studies (phase II randomized and phase III), 14 moderately well-designed studies that account for most common biases (matched cohort and phase II studies), 28 studies with design limitations (retrospective reviews), and 1 reference meta-analysis. CONCLUSIONS:This systematic review and guidelines provide up-to-date recommendations focusing on recent advancements for adjuvant treatment of resected PDAC using modern systemic therapy regimens and selective use of radiotherapy using modern techniques.

TPS843 Background: Black individuals, including African Americans, experience a disproportionate cancer burden and exhibit the lowest survival rates among all racial groups for gastrointestinal (GI) cancers. The EQUITY GI study seeks to address the significant health disparities encountered by Black patients with GI cancers in the areas of biomarker testing, evidence-based care, clinical trial participation, and health literacy. Our central hypothesis postulates that a comprehensive approach—encompassing appropriate biomarker testing, ensuring evidence-based treatments, support for clinical trial participation, and health literacy initiatives—is essential to effectively mitigate health disparities among Black patients with GI cancers. Methods: The primary objective of this study is to promote equitable care for Black patients with GI cancers by ensuring appropriate biomarker testing and the delivery of evidence-based care. The secondary objectives include promoting clinical trial participation and enhancing health literacy. The specific goals are to increase the rate of evidence-based care, including biomarker testing, to ≥80%, increase the clinical trial enrollment rate from 5% to 15%, and improve the Cancer Health Literacy Test-30 (CHLT-30) score by 30%. Following a comprehensive assessment of the care gap, several initiatives will be implemented: 1. Tracking biomarker testing through a clinical information tracking tool (EQUITY-GI Oncotracker), 2. Providing guidance to treating providers through a molecular tumor board, 3. Facilitating referrals for clinical trials through navigators, and 4. Implementing health literacy interventions measured by CHLT-30 score. We aim to enroll 200 patients over 18 months. With this expected enrollment, the power to detect a ≥60% absolute improvement in the biomarker testing rate (from the current 20% to the expected ≥80%) is over 98%, using a two-sided chi-square test with a significance level of 0.05. To demonstrate an improvement in the clinical trial enrollment rate from 5% to 15%, 18 black patient will be required to get enrolled in a clinical trial through the referrals generated from the current project. To detect a 30% improvement in the mean CHLT-30 score (17 to 22) following health literacy interventions, at least 120 patients will be required, using a two-sided paired t-test with a significance level of 0.05.

644 Background: There is limited data to guide surveillance in biliary tract cancers (BTCs) following resection. Minimal residual disease (MRD) assays utilize circulating tumor DNA (ctDNA) to detect early recurrence. Current data is limited on the use of ctDNA in biliary tract cancers in conjunction with surveillance imaging. In this study, we aim to elucidate the role of ctDNA monitoring in patients with biliary tract cancers who have undergone curative resection. Methods: We conducted a retrospective search at a tertiary care and several satellite settings to identify patients with BTCs who underwent curative surgery and subsequently had ctDNA monitoring. We collected demographic variables, disease characteristics, treatment regimens, and follow-up data. The primary endpoint of the analysis is recurrence-free survival (RFS), comparing patients with detectable ctDNA to those with negative ctDNA post-surgery. Kaplan-Meier analysis and Log-Rank tests were performed to evaluate RFS, and Cox proportional hazards(PH) models were employed for both univariate and multivariate analyses. Results: We identified 36 pts with a median age of 72 (34-87) yrs at diagnosis. In this study cohort, 22 (59%) were female, 32 (88%) were white, and 3 (8%) were African American. 12 (33%) pts were ctDNA positive at any point during surveillance, while the remainder were ctDNA negative. In the ctDNA-positive group, recurrences developed in 7 out of 12 (58%) pts. In the ctDNA negative group, only 2 out of 24 (8.3%) pts developed recurrences. The median time to recurrence following primary surgery was 10.7 months, while the time to ctDNA positivity following surgery was 7.8 months. The median time from ctDNA positivity to recurrence was 1.1 months. Pts with ctDNA positivity had a significantly lower 1-year RFS of 47.62% (95% CI: 7.5%-81%) compared to those with ctDNA negativity (85%, 95% CI: 60%-95%; p = 0.0008). Multivariate analysis demonstrated that ctDNA positivity at any point was associated with a significantly higher risk of recurrence (HR: 21.8, 95% CI: 2.3–203, p<0.0001). Conclusions: In pts with BTCs who underwent resection, ctDNA testing had independent prognostic value. Further prospective trials are needed to help define the role of ctDNA in this patient population. Baseline demographics and clinical characteristics of patients who were ctDNA positive vs. negative. Characteristics Patients with Biliary Tract Cancers who were ctDNA positive Patients with Biliary Tract Cancers who were ctDNA negative N 12 24 Age in years, median (range) 72 (62 – 87) 72 (34 - 85) Sex n (%) Male 7 (58) 8 (33) Female 5 (42) 16 (67) Race n (%) White 12 (100) 20 (83) Black/African American 0 (0) 3 (13) Asian 0 (0) 1 (4) Primary Tumor Location n (%) ICC 4 (33) 11 (46) ECC 4 (33) 5 (21) GBC 2 (17) 6 (25) AC 2 (17) 2 (8) Margin Status n (%) Positive 2 (17) 3 (13) Negative 10 (83) 21 (87) Clinical Stage I 0 (0) 1 (4) II 2 (17) 12 (50) III 8 (66) 10 (43) IV 2 (17) 0 (0) Unknown 0 (0) 1 (3)

BACKGROUND:Multimodality therapy incorporating a combination of cytoreductive surgery (CRS), intraperitoneal (IP) and systemic therapy continues to evolve for peritoneal carcinomatosis (PC) However, treatment and outcomes vary depending on tumor of origin. AIMS:To develop Appropriate Use Criteria (AUC) guidelines to facilitate treatment decision-making for patients with PC based on available evidence. MATERIALS AND METHODS:The American Radium Society (ARS) multidisciplinary expert panel performed a comprehensive systematic review. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) methodology was used. These studies were used to inform the expert panel, which then rated the appropriateness of various treatments in seven representative clinical scenarios through a well-established modified Delphi consensus methodology. RESULTS:Treatment of PC is often treated with a combination of CRS and IP ± systemic chemotherapy but specific recommendations exist for different tumor types and outcomes vary. DISCUSSION:Treatment of PC is complex and varies depending on origin of primary tumor and extent of disease. These AUC assist in patient and treatment selection for different clinical scenarios. CONCLUSION:A summary of recommendations is outlined to guide practitioners on the management of PC from different tumor origins.

TPS516 Background: Esophageal adenocarcinoma (EAC) is the seventh most common cancer globally and ranks sixth in overall mortality. Despite improvements in pre-operative therapy, EAC has a high recurrence rate, especially among patients whose tumors do not achieve pathologic complete response (pCR), thus there is a critical need to enhance pCR rate and improve long-term outcomes. We recently discovered that a subset of EACs are driven by tumor-intrinsic oncogenic TGFβ signaling and have identified two potential biomarkers to predict response to anti-TGFβ therapy. One of these biomarkers is enriched in poorly differentiated EAC. We hypothesize that TGFβ signaling blockade will exert a tumor-inhibitory effect in patients with EAC and propose a double window-of-opportunity trial to test if TGFβ receptor I inhibitor vactosertib can improve pCR and induce tumor metabolic response in patients undergoing neoadjuvant therapy for localized EAC. Methods: This phase II double window of opportunity study assesses the efficacy and pharmacodynamics of the oral TGFβ Receptor I inhibitor vactosertib in patients with locally advanced esophageal adenocarcinoma (EAC). Patients will be treated with single-agent vactosertib in two windows of opportunity: the first will be prior to initiation of standard of care neoadjuvant therapy and the second after completion of neoadjuvant therapy prior to surgery. Patients will be eligible if they have poorly differentiated EAC and are appropriate for neoadjuvant therapy followed by resection as per standard of care. The primary objectives are improvement in pCR compared to historical controls and metabolic response (decrease in fluorodeoxyglucose uptake by PET CT) in the primary tumor after the first window. Secondary objectives will evaluate biomarkers of response identified in preclinical studies. Pre- and post-first window of opportunity treatment biopsies will be obtained for correlative and exploratory analyses. Clinical trial information: NCT06044311 .

7 Background: Mitomycin (MMC) is used concurrently during chemoradiation (CRT) treatment for non-metastatic anal squamous cell carcinoma (SCCA). The most effective dosing of MMC is not established, and due to concerns for tolerability, many have adopted a dose-reduction strategy. This study evaluates differences in treatment response and recurrence between MMC dosing in this setting. Methods: Demographics, age, smoking history, staging, and treatment history were collected for patients with non-metastatic SCCA treated with CRT from January 2011-September 2024 at a tertiary cancer center. Chi-square analyses compared categorical variables, and ANOVA tests were used to compare treatment response and recurrence between 3 MMC doses (12mg/m 2 x 1 dose with cap of 20mg, 10mg/m 2 x 2 doses, 10mg/m 2 x 1 dose). Results: There were 124 patients, 6 of whom were excluded due to lack of follow up. Of the 118 included, 70% were female, 16% Black, 3% Hispanic/Latino, and 58% current/former smokers. Median age was 61 years (31-98). Thirty-three (28%) pts were treated with MMC 12mg/m 2 , 71 (60%) with 10mg/m 2 x2 doses, and 14 (12%) with 10mg/m 2 x1 dose. Stage I included 18% of 12mg/m2, 7% of 10mg/m 2 x2 doses, and 7% of 10mg/m 2 x1 dose; stage II included 18% of 12mg/m2, 37% of 10mg/m 2 x2 doses, and 50% of 10mg/m 2 x1 dose; stage III included 64% of 12mg/m2, 56% of 10mg/m 2 x2 doses, and 43% of 10mg/m 2 x1 dose. A total of 39.7% were treated with MMC/capecitabine and 60.3% with MMC/fluorouracil. Complete response was achieved in 91% receiving the 12mg/m 2 , 75% receiving 10mg/m 2 x2 dose, and 71% receiving 10mg/m 2 x1 dose (p=0.13, Table 1). Using logistic regression with MMC dose, stage, age, and smoking status as independent predictors, the odds of achieving complete response were lower in 10mg/m 2 x2 doses (p=0.03) and 10mg/m 2 x1 dose (p=0.03) compared to 12mg/m 2 . Local, regional, or metastatic recurrence occurred in 15% of pts receiving 12mg/m 2 , 17% of 10mg/m 2 x2 doses, and 7% of 10mg/m 2 x1 dose. No significant difference was seen in local (p=0.52), regional (p=0.93), metastatic (p=0.87), or overall recurrence (p=0.65) between the MMC doses. Conclusions: Odds of achieving complete response was greater with 12mg/m 2 dosing. Local, regional, and metastatic recurrence were similar among the different MMC dosing cohorts. Differences in tolerance and side effects should be delineated to guide individualized dosing of MMC.

8 Background: Advanced-stage squamous cell carcinoma of the anus (aSCCA) is a rare malignancy. Diagnostic biopsies are often inadequate for tissue-based genomic profiling, thus genomic profiles are largely unexplored in this setting. We assessed liquid biopsy NGS results of aSCCA patients (pts) and described genomic profiles by age and sex. To our knowledge, we are the first to describe genetic alterations by liquid biopsy in this patient population. Methods: Pts with aSCCA who underwent circulating tumor DNA (ctDNA) NGS with Guardant360 assays from 2017 to 2024 were included. Frequency of alterations were assessed based on sex and age (18-49 years (yrs), ≥50 yrs). Co-occurrence patterns were assessed using cBioPortal. Demographics were extracted from test requisition forms. Statistical analyses via two sided t-tests were performed with significance defined as p<0.05. Results: 646 pts with aSCCA had non-synonymous ctDNA alterations detected; 69.2% (N=447) were female and 30.8% (N=199) male. Median age was 66 yrs (32-94) with 9.9% (N=64) <50 yrs and 90.1% (N=582) ≥50 yrs. Most frequently altered genes were PIK3CA (17.3%), TP53 (9.8%), ATM (7.8%), EGFR (4.3%), and BRCA2 (4.2%). More unique genes were altered in ≥50 yrs cohort [53 mutations, 38 genes with copy number amplification (CNA)] vs <50 yrs cohort (30 mutations, 66 CNA). Most frequent genes altered in <50 yrs cohort were TP53 (17.6%), PIK3CA (13.2%), EGFR (11.0%), APC (4.4%), and MET (4.4%). PIK3CA (16.7%), TP53 (12.2%), ATM (8.8%), BRCA2 (5.5%), and EGFR (3.4%) were most frequent in ≥50 yrs cohort. More genes were altered in females (64 mutations, 32 CNA) vs. males (56 mutations, 41 CNA). Most frequent alterations in females were PIK3CA E545K (3.4%), PIK3CA CNA (2.8%), PIK3CA E542K (1.9%), and ATM CNA (1.0%) vs in male pts being PIK3CA E545K (4.8%), PIK3CA CNA (3.3%), PIK3CA E542K (3.3%), EGFR CNA (1.6%), TERT promoter (1.0%). Overall, PIK3CA and TP53 alterations were mutually exclusive (odds ratio 0.43, p<0.001). Conclusions: Liquid biopsy is feasible in patients with aSCCA. Most frequently detected alterations and CNAs were in PIK3CA and TP53 in aSCCA which is consistent with prior studies evaluating aSCCA tumor NGS in tissue-based assays. Alterations varied across age and sex. PIK3CA E545K and E542K alterations were detected frequently in this population and have on-label therapies for non-aSCCA indications which may be a source for clinical consideration in this cancer type in the future. This data illustrates the importance of liquid biopsy NGS to also screen for clinical trial enrollment in a disease which is poorly responsive to standard therapy. Additional research is warranted to further elucidate genomic profiles for clinical applications of this rare tumor.

Objectives: Cervical esophageal cancer (CEC) is an uncommon malignancy accounting for <5% of all esophageal carcinomas. Treatment of CEC varies and is adapted from established regimens used for squamous cell carcinoma (SCC) or the lower esophageal and head and neck. The present systematic review and guidelines are intended to assist treatment decision making for patients with CEC based on the available evidence. Methods: Using the Population, Intervention, Comparator, Outcome, Timing, and Study Design (PICOTS) framework, the evidence regarding treatment outcomes was assessed using Cochrane and PRISMA 2020 methodology. Eligible studies included prospective Phase II to III trials and retrospective analyses published between January 1, 2013 and February 23, 2024 in the Ovid Medline database. These references were assessed through the American Radium Society (ARS) Appropriate Use Criteria (AUC) methodology. A systematic review PRISMA 2020 checklist confirmed the completion of essential elements. RAND-UCLA consensus methodology was used by the expert panel to rate the appropriateness of the treatment options. Results: ARS AUC recommendations include (1) larynx preservation using endoscopic resection (EMR or ESD) alone for the typical case with pT1a cN0 cM0 CEC, (2) definitive CRT for the typical case with cT1bN0M0 in patients who cannot undergo endoscopic resection, (3) larynx-preserving using definitive CRT (with or without induction chemotherapy) for the typical case with nonmetastatic locally advanced CEC (advanced T-stage tumors or involved lymph nodes), with surgery reserved for those patients with incomplete response or locoregional recurrence. Conclusions: This ARS AUC summary provides guidelines for the management of SCC of the cervical esophagus provides based on available evidence. Topics that warrant further investigation include optimization of (1) patient selection; (2) multimodality therapies including chemotherapy, immunotherapy, and targeted agents; (3) radiation dose, schedule, and treatment volume; and (4) supportive care for patients with CEC. Ongoing trials continue to improve outcomes for patients with CEC.

Adoptive cellular therapy, or the collection and transfer of immune cells to patients, is emerging as a treatment option for many malignancies, especially hematologic malignancies, with a growing role in solid tumors and non-malignant conditions such as autoimmune diseases. The adoptive transfer of the innate immune cell natural killer (NK) cells is uniquely poised as a potential therapy alone or as an adjunct to other immune-targeted therapies for patients with cancer, with several advantages over other cell therapies such as T cells. We review key concepts in NK cells as a therapy for human disease and discuss key trials using NK cells in malignancy.

OBJECTIVES:Esophageal cancer (EC) often presents with dysphagia due to tumor obstruction. Esophageal stenting has the potential of palliating dysphagia, improving nutrition, preventing aspiration, and improving quality of life (QoL) but may be associated with risks. The present systematic review and guidelines are intended to assist treatment decision-making when considering stent placement in patients with EC based on the available evidence. METHODS:Using the population, intervention, comparator, outcome, timing and study design framework, the evidence was assessed using Cochrane and PRISMA 2020 methodology. Eligible studies included prospective phase II-III trials and retrospective analyses published between January 1, 2010 and December 3, 2024 in the Ovid Medline database. These references were assessed by American Radium Society (ARS) Appropriate Use Criteria (AUC) methodology. RAND-UCLA consensus methodology was used to rate the appropriateness of the use of stents. RESULTS:ARS AUC recommendations include (1) esophageal stenting is usually not appropriate in patients with early-stage EC in whom upfront surgery is planned; (2) esophageal stenting is usually not appropriate in patients with locally-advanced EC in whom neoadjuvant/perioperative therapy and esophagectomy or definitive chemoradiation is planned; (3) esophageal stenting may be appropriate in the setting of metastatic EC, especially in patients with short life expectancy with limited treatment options; (4) esophageal stenting is usually not appropriate for benign stricture following curative-intent therapy; (5) esophageal stenting is usually not appropriate for locally recurrent tumor in the setting of prior radiation; and (6) esophageal stenting is usually appropriate for management of tracheoesophageal fistula before curative-intent treatment. CONCLUSIONS:This ARS AUC summary provides guidelines for the use of esophageal stents in patients with EC provides based on available evidence.

836 Background: Circulating tumor DNA (ctDNA) has a short half-life (<2 hours) which may permit real-time monitoring of tumor status. This single-institution study aimed to assess the feasibility of rapid treatment response evaluation through serial short-interval ctDNA testing. Methods: Patients with gastrointestinal (GI) cancer undergoing immune checkpoint inhibitor (ICI)-based therapy were included. A personalized, tumor-informed ctDNA assay (Signatera, Natera, Inc.) was used in this study. We collected samples to measure the baseline ctDNA levels on cycle 1, day 1 (C1D1) of treatment or within 14 days prior to C1D1. A second ctDNA sample was obtained after 14-21 days depending on the cycle length of the treatment regimen employed (on cycle 2, day 1 [C2D1]). Changes in ctDNA levels between baseline and C2D1 were recorded, as well as the tumor response at the first radiographic assessment. Patients achieving partial response (PR) or better, or stable disease (SD) with tumor shrinkage supporting continuation of same treatment were considered responders. Results: The study cohort consisted of 14 patients aged 36-89 years (median age 66); 5 patients were female. Tumor types included advanced colorectal (n=5) and gastroesophageal (n=9) cancers. Treatments consisted of pembrolizumab alone (n=5), ICI + chemotherapy combinations (n=8), and regorafenib plus nivolumab (n=1). Baseline ctDNA levels were obtained on C1D1 in 9 patients, with the remaining 5 patients having baseline measurements within 14 days before C1D1. All patients had the second ctDNA level drawn on C2D1. The median interval between C1D1 and the first radiographic response assessment was 61 days (range, 45-84). A reduction in ctDNA levels by 50% or more (range: 66-100%) was observed in 9 patients (64%) after one cycle of treatment. All 9 patients were classified as responders at the time of first radiographic assessment: 7 with PR and 2 with SD but significant tumor shrinkage leading to continuation of the same treatment. In 3 patients (21%), ctDNA levels increased (range: 20-500%), correlating with progressive disease (PD) on first assessment scan. Two patients showed increased ctDNA levels of 82% and 22% after one cycle of treatment but achieved PR and SD, respectively. In both patients, however, the 3rd ctDNA level drawn before the first assessment scan dropped by >90%. Overall, short-interval ctDNA kinetics correlated with treatment response in 12 of 14 patients (86%), with a binomial test p = 0.0065. Conclusions: Short-interval ctDNA kinetics demonstrates a strong correlation with radiographic tumor response and clinical benefit in GI cancer patients receiving ICI-based treatments, providing early signal of tumor response. This approach has the potential to guide treatment decisions if validated in larger prospective studies.

BACKGROUND:Hepatic artery infusion with floxuridine is a treatment option for patients with colorectal liver metastases or intrahepatic cholangiocarcinoma. Outcomes from newer centers are understudied. Predictive markers are needed, and quantitative circulating tumor DNA is an emerging candidate method for predicting response in patients receiving hepatic artery infusion. We aimed to describe safety, feasibility, early oncologic outcomes, and quantitative circulating tumor DNA dynamics in patients treated with hepatic artery infusion at a newly established program. METHODS:Single-institution analysis of patients who underwent hepatic artery infusion pump placement (April 2022-April 2024) was conducted. Primary outcomes included safety and feasibility (receiving ≥1 cycle of floxuridine). Secondary outcomes included radiographic response (Response Evaluation Criteria in Solid Tumors 1.1), relative dose intensity of floxuridine received, and quantitative circulating tumor DNA response. RESULTS:A total of 36 patients underwent hepatic artery infusion pump placement (colorectal liver metastases: 32; cholangiocarcinoma: 4). Technical success was 100%. Feasibility was 97%. One patient experienced mortality at 90 days from disease progression. Three patients (8%) experienced a total of 5 hepatic artery infusion pump-specific complications (pump pocket [n = 3], hemorrhage [n = 1], biliary sclerosis [n = 1]). Median relative dose intensity was 68.5% (colorectal liver metastases: 68.3%; cholangiocarcinoma 72.5.0%). For the 27 patients who underwent floxuridine therapy with available postoperative imaging, disease control rate was 97% (partial response: n = 15; stable disease: n = 11). Quantitative circulating tumor DNA was obtained from 16 patients (44%). Circulating tumor DNA dynamics appeared to correlate with and precede radiographic response. CONCLUSIONS:Implementation of a new hepatic artery infusion program is safe and feasible with promising early oncologic outcomes. Circulating tumor DNA tracking is achievable and dynamic changes in circulating tumor DNA may correlate with radiographic response to treatment.

TPS794 Background: Pancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis, with a 34% 5-year survival rate for patients with localized disease. Guidelines recommend consideration of neoadjuvant approaches in localized PDA with the goals of controlling microscopic metastatic disease and increasing rates of microscopically margin-negative resections. One of the hallmark characteristics of PDA is a micronutrient poor, highly stromal microenvironment. Surviving in this environment requires enhanced mitochondrial function, which utilizes isocitrate dehydrogenase 1 (IDH1). In pre-clinical studies, ivosidenib, an FDA approved medication for IDH1 mutant AML, induced high levels of reactive oxygen species in PDA cells with wild-type IDH1, and caused tumor regressions and extended survival in implanted KPC mouse models. Here, we investigate the addition of ivosidenib to standard of care neoadjuvant mFOLFIRINOX in patients with resectable PDA to determine safety, pharmacodynamics, and early efficacy signals. Methods: This is a phase I, single-center, open label, dose de-escalation and expansion study in patients with resectable PDA. Eligible patients must have histologically confirmed and resectable right-sided PDA based on CT or MRI imaging. Patients receive approximately 10 weeks of neoadjuvant treatment composed of 2 weeks of ivosidenib monotherapy, followed by 6 weeks (3 cycles) of mFOLFIRINOX with ivosidenib, followed by up to 4 weeks of ivosidenib monotherapy until the day of surgery. Ivosidenib is administered once daily at 500mg; it is to be de-escalated to 250mg based on Bayesian Optimal Interval Design with Informative Prior and a target dose limiting toxicity (DLT) rate of 30%. The primary endpoint is to determine the safety and tolerability of ivosidenib in combination with mFOLFIRINOX. Secondary endpoints include RECIST version 1.1 response rates, major pathologic response rates, and biochemical (CA19-9, CEA) response rates. Correlative studies will be performed on surgical samples to evaluate metabolomic profiles. At the time of submission, 10 out of 16 planned patients have been enrolled. There have been no DLT at 500mg of ivosidenib. Clinical trial information: NCT05209074 .