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Abstract Background: Despite its widespread adoption, there is a lack of data as to whether breast MRI for local staging and surgical planning of newly diagnosed breast cancer patients improves oncologic outcomes. The Alliance A011104 phase III trial was designed to test the hypothesis that MRI detection of mammographically occult disease helps to tailor surgical intervention thereby reducing local recurrence and improving local regional control. Here we report on the primary outcome of 5-year local regional recurrence. Methods: Patients with newly diagnosed clinical stage I-II, ER/PR- and HER2- negative (triple- negative) or ER/PR-negative and HER2-positive breast cancer, deemed eligible for breast- conserving surgery (BCS) based on clinical exam, mammography +/- ultrasound were randomized to undergo staging breast MRI or no further local staging. Patients with multifocal tumors that could be encompassed in a single operative resection were eligible. Patients who were carriers of gBRCA 1/2, or who had bilateral breast cancer, or a prior history of breast cancer were excluded. Initial eligibility was limited to patients not scheduled to receive neoadjuvant chemotherapy; however, a subsequent amendment allowed for enrollment after completion of neoadjuvant chemotherapy. Categorical variables were compared between arms with a chi-square or Fisher’s exact test. LRR, distant recurrence and overall survival (OS) were estimated with Kaplan-Meier point estimates and 95% confidence intervals (CIs). Hazard ratios (HRs) and 95% CIs were obtained from Cox proportional hazards models. Results: Of 319 patients enrolled from 2/2014-12/2019,161 were randomized to undergo breast MRI and 158 to no breast MRI evaluation. The mean age at enrollment was 58.9 years (range 29-85). Most patients (72.1%) had T1 tumors, 93.4% were cN0 and 19.7% were HER2 positive. Systemic chemotherapy was utilized in 85% with 17.6% receiving treatment neoadjuvantly; receipt of systemic therapy was unknown for 15 patients (4.7%). Two hundred and ninety-eight patients (93.4%) underwent surgical intervention; 91.9% underwent BCS as initial surgical procedure with no significant differences noted between groups (92.7% in the no MRI group and 91.9% in the MRI group [p=0.62]). Of patients who underwent breast surgery, 293 underwent axillary evaluation with the majority (270 patients, 92%) undergoing sentinel lymph node biopsy as the only axillary intervention. Among patients who received neoadjuvant chemotherapy, the overall pathologic complete response rate was 39.3%, 29.0%in the MRI arm vs. 52.0% no MRI arm (p=0.10). Receipt of adjuvant radiation was comparable between arms, 85.4% and 85.0% receiving radiation in the no MRI and MRI arms, respectively. Among 298 patients evaluable for the primary endpoint, with median follow-up of 61.1 months (0.2, 68.1), there were no differences in rates of LRR; 5-year local regional control was 93.2% (89.0-97.6%) in the MRI group and 95.7% (92.3-99.1%) in the no MRI group (HR: 1.1, 95% CI: 0.3, 3.9). For the entire cohort, 5-year distant recurrence-free rate and OS were 94.3% (91.7, 97.1) and 92.2% (89.1, 95.4), respectively, with no differences between groups. Conclusions: With multimodality therapy, rates of 5-year LRR in patients with early stage triple- negative and HER2-positive breast cancer are very low. Breast MRI for local staging and surgical planning in this setting does not result in improved local regional control. Support: U10CA180821, U10CA180882; UG1CA189823; U10CA180868 (NRG Oncology); ClinicalTrials.gov Identifier: NCT01805076; https://acknowledgments.alliancefound.org Citation Format: I. Bedrosian, K. Ballman, L. M. McCall, C. E. Comstock, G. W. Unzeitig, T. Yen, A. Weiss, B. G. Haffty, J. M. Bensenhaver, S. M. DeSnyder, J. J. Liu, A. H. Partridge, L. A. Carey, K. K. Hunt.Effect of Preoperative Breast MRI Staging on Local Regional Recurrence (LRR) in Early Stage Breast cancer: Alliance A011104/ACRIN 6694 [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr GS2-07.

ABSTRACT Background Sex‐specific medicine (SSM) is increasingly recognized as vital for patient care yet remains underrepresented in graduate medical education curricula. Traditional didactics and workshops have limited reach at national conferences. Gamification has emerged as a strategy to increase engagement, though its use in professional networking and conference settings is not well described. Methods The Resident and Medical Student (RAMS) Hunt is a novel, gamified, team‐based event incorporating topics in SSM, health equity, and professional development. The Hunt was implemented at three consecutive Society for Academic Emergency Medicine (SAEM) Annual Meetings (2023–2025). At each conference, teams visited four city landmarks, completing content‐based challenges at each site. Post‐event surveys assessed enjoyment, perceived educational effectiveness, and design preferences. Quantitative data were summarized descriptively, and qualitative responses underwent thematic analysis. Future iterations will include pre‐ and post‐event knowledge and attitude assessments to enhance rigor. Results Across three Hunts, more than 66 teams registered, and there were 88 completed surveys (Austin 2023 n = 23; Phoenix 2024 n = 48; Philadelphia 2025 n = 17). Mean enjoyment ratings were 4.52, 4.44, and 3.47 (out of 5), respectively. Perceived educational effectiveness ratings were 4.09, 4.11, and 3.47. Participants reported that ideal numbers of challenge sites and participants per team were 3–4. Qualitative themes highlighted enhanced awareness of how biological sex and sociocultural attributes influence health outcomes, the value of interactive learning, and networking opportunities. Logistical barriers included registration, inclement weather including a downpour in Philadelphia, and course navigation. Conclusions The RAMS Hunt demonstrated feasibility and strong learner engagement in disseminating SSM content through a novel conference‐based gamification model. This innovation offers a replicable framework for integrating experiential, team‐based learning into professional society meetings. Opportunities remain to hone game logistics to enhance sustainability and broader adoption. Future evaluations will include objective measures of learning and knowledge retention.

Purpose: A variety of care pathways are offered to females with chronic pelvic pain (CPP) and pelvic floor myofascial pain (PFMP), which may affect treatment outcomes. This study aims to compare care pathways and describe health care utilization and characteristics of patients with CPP and PFMP referred for physical therapy (PT) at a tertiary care center. Methods: A retrospective cohort analysis was conducted on females with CPP and PFMP referred for PT. Patients received PT, medication management, injection therapy, or a combination of treatments. We collected data on health care utilization, comorbidities of interest, and patient-reported outcome measures (PROMs). Wilcoxon rank-sum tests were used to compare patients with pre- and posttreatment PROM scores. Results: A total of 1172 patients were referred for PT treatment, but 19.5% (n = 229) did not attend any PT sessions, and only 18% (n = 211) of patients attended the recommended number of PT sessions. Comorbid urinary (48.5%, n = 569) and bowel dysfunction (43%, n = 512) were prevalent. Patients consulted with multiple providers. Most patients (57.1%, n = 669) utilized opioid medications. Less than 20% completed both pre-and posttreatment PROMs. Discussion: Care pathways vary widely for the treatment of PFMP. Low adherence to PT and a trend toward greater than 5 subspecialty appointments indicating higher health care utilization reflect the range of inconsistent patient experience likely affecting outcomes. Outcomes of care are uncharted territory. Optimal care pathways for CPP and PFMP need to be established, along with further investigation of PROMs, to determine which treatments result in effective outcomes that matter to patients.

162 Background: In preclinical studies, the tryptophan-metabolizing enzyme, Indoleamine 2, 3-dioxygenase 1 (IDO1), promotes resistance to radiation in colorectal cancer, and IDO1 inhibition with epacadostat improves tumor radiosensitivity. In a phase 1 trial, patients (pts) with locally advanced rectal cancer (LARC, n=17) were treated with epacadostat in combination with short course radiotherapy (SCRT) and CAPOX which was well-tolerated, and the recommended phase 2 dose (RP2D) of epacadostat was 400mg BID. Here we report efficacy and safety from the NCI-supported phase 2 (NCT03516708) multicenter, open-label trial (treatment cohort). Methods: Pts were treated with standard of care (SOC) SCRT, then SOC neoadjuvant chemotherapy (NAC) followed by SOC surgical resection or non-operative management (NOM). Epacadostat (400 mg BID) started with SCRT and continued until starting NAC (a minimum of 21 days). Eight pts were enrolled prior to discontinuation of epacadostat by Incyte in February/March 2025. The primary endpoint is Neoadjuvant Rectal (NAR) score. In patients who underwent NOM, we calculated MRI-based tumor regression grade (MR-TRG). Secondary endpoints are pathologic complete response (pCR) rate, complete clinical response (cCR) rate, and progression free survival (PFS). Results: Table 1 summarizes baseline characteristics and endpoints (primary and secondary). NOM was pursued in 7/8 (87.5%) pts, surgical resection was performed on 1/8 (12.5%). At median follow-up of 12 months, local tumor regrowth occurred in 1 pt initially treated with NOM (after tumor regrowth, he underwent salvage surgery and is currently on surveillance). Treatment with epacadostat was interrupted in 2/8 (25%) patients due to grade 3 maculopapular skin rash. Most frequent treatment-emergent adverse events (TEAEs) regardless of causality (all grades (G)/G3-4) were bloating (75%/0%), increased ALT (62.5%/0%), increased AST (50%/0%), nausea (50%/0%), and constipation (50%/0%). Grade 3 diarrhea and grade 3 non-cardiac chest pain occurred in 1 patient each (both unrelated to epacadostat). Conclusions: Epacadostat demonstrates promising efficacy and manageable safety in patients with LARC. The biomarker cohort and correlative studies are ongoing. Clinical trial information: NCT03516708 . Baseline characteristics and endpoints. Patient Age Sex Ethnicity Stage Surgery/NOM NAR MR-TRG cCR/pCR Recurrence 1 52 M Caucasian T3N1 NOM NA 2 Y/NA No 2 45 M Caucasian T3N1 NOM NA 3 Y/NA Local tumor regrowth 3 48 M Caucasian T3N2 NOM NA 3 Y/NA No 4 61 M Caucasian T4N2 NOM NA 3 Y/NA No 5 57 M Caucasian T3N0 NOM NA 1 Y/NA No 6 60 F Caucasian T3N1 Surgery 15 3 N/ypT3N0 No 7 67 M Caucasian T4N0 NOM NA 3 Y/NA No 8 51 M Caucasian T4N2 NOM NA P NA No

Background/objectives: Improvements in esophageal adenocarcinoma (EAC) treatment have reduced mortality. While chemoradiation before surgery was previously a standard of care, updated guidelines recommend peri-operative chemotherapy without chemoradiation. Continued investigation into optimal non-operative treatment paradigms for patients who defer surgery or are not candidates for surgery and certain chemotherapy regimens is needed. The impact of induction chemotherapy prior to chemoradiation on survival and surgical outcomes remains unclear. This study assessed survival and surgical outcomes in a real-world cohort of EAC patients receiving induction chemotherapy before chemoradiation. Methods: This single-institution, IRB-approved, retrospective cohort study included patients with newly diagnosed stage II-IVb (oligometastatic for IVb) EAC who received definitive chemoradiation (radiation ≥ 40 Gy and two cycles of chemotherapy) +/− esophagectomy from 2007 to 2022. Patients receiving induction chemotherapy were compared to those who did not. Endpoints included survival and surgical outcomes. Results: A total of 141 EAC patients received definitive chemoradiation; 83 received induction chemotherapy before chemoradiation. Patients receiving induction chemotherapy were younger (p < 0.01) with slightly lower performance status (p = 0.27) and presented at a more advanced stage (p < 0.001). Median OS was 3.5 years in the induction chemotherapy group compared to 2.2 years (p = 0.10). There was no difference in pathologic complete response (p = 0.81), esophagectomy frequency (p = 0.87), or surgical downstaging between treatment groups (p = 0.84). Conclusions: In this real-world, single-institutional patient cohort investigating induction chemotherapy prior to chemoradiation in EAC, patients receiving induction chemotherapy did well but did not have a statistically significant improvement in survival outcomes or surgical outcomes. This study showed that significant numbers of real-world patients may not receive esophagectomy. Thus, prospective, randomized clinical trials are warranted to better delineate the efficacy and selection of patients for induction chemotherapy when non-operative approaches are favored.

Abstract Pain medicine triage plays a crucial role in ensuring patients receive timely and appropriate care by scheduling them to the most suitable treatment path. However, the absence of standardized triage protocols in pain medicine often leads to inefficiencies, including delay of care and wastage of healthcare resources. This study aims to develop a rule-based automated referral triage system leveraging information from patients' medical notes for scheduling patients to specific procedures in the pain medicine department. The proposed triage system, grounded in the knowledge and expertise of clinical providers, processed referral order comments and referring provider notes by iteratively refining the Natural Language Processing (NLP) rules and post-processing rules through intensively reviewing 76 patients. A post-processing regression model was incorporated to further enhance the accuracy. To ensure alignment with real-world practices, the system was integrated into an electronic health record (EHR) platform for real-time application, streamlining scheduling workflows and enhancing usability in daily clinical settings. After three iterations, the proposed NLP and post-processing rules improved accuracy from 76.3 to 80.3% compared to machine learning (ML) approaches in the preliminary study. The post-processing model further increased accuracy to 84.2%. The implementation accuracy of 200 cases for the first 3 months was consistent with our prediction at 83.5%, which concluded that the improvement over ML models (p-value = 0.018) was statistically significant at 95% significance level. This study demonstrates the feasibility and benefits of a knowledge-driven approach to referral triage in specialized medical fields. It lays a foundation for others in building similar triaging solutions to other specialties.

BACKGROUND Among antiretroviral therapy–suppressed (ART-suppressed) people with HIV (PWH), women have higher levels of some inflammatory markers than men, but the effect of sex on the inflammatory proteome, and whether age modifies these differences, remain unclear. METHODS Plasma inflammatory protein levels were assessed in ART-suppressed PWH from the Center for AIDS Research Network of Integrated Clinical Systems. The relationship between sex and plasma proteins — including 22 interferon-α response pathway proteins — was assessed, adjusting for confounders and assessing interactions by age. RESULTS Of 922 participants, 162 (18%) were female. The median age was 47, above which the majority of women had undetectable plasma anti-Müllerian hormone levels, a biomarker of ovarian reserve. Age modified the influence of sex on the inflammatory proteome. Older age (>47) was associated with greater increases among women than men in 194 proteins. Interferon-α response proteins were higher in men in those ≤ 47 but higher in women in those > 47 (interaction P < 0.001). Among the 131 proteins associated with mortality risk ( q < 0.05), only 5 differed by sex among those ≤ 47, while 79 differed by sex in those > 47, with nearly all being higher in women. Women had decreased mortality than men ≤ 47 ( P < 0.001) but had similar mortality > 47 ( P = 0.84). CONCLUSION The menopausal transition appears to increase systemic type I interferon responses and inflammation in women with HIV, which may contribute to a loss of female advantage in mortality. FUNDING NIH National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke; National Institute of Allergy and Infectious Diseases.