Kim, Sung Hyun

Abstract Background: Understanding the spatiotemporal dynamics of the tumor microenvironment (TME) during treatment is crucial for improving outcomes in pancreatic ductal adenocarcinoma (PDAC). This study presents a pre-planned spatiotemporal analysis from a phase II trial evaluating neoadjuvant mFOLFIRINOX in resectable PDAC, aimed at elucidating treatment resistance mechanisms and identifying predictive biomarkers. Methods: This multi-institutional, single-arm phase II trial enrolled treatment-naïve patients with histologically confirmed resectable PDAC (NCT05066802) who underwent six cycles of neoadjuvant mFOLFIRINOX followed by surgery. The primary endpoint was the R0 resection rate. Matched pre-treatment tumor biopsies and post-treatment surgical specimens were analyzed from selected responders (R) and non-responders (NR) using high-resolution spatial transcriptomics (10X Genomics Visium). This approach enabled comprehensive mapping of TME evolution and treatment-induced changes. Results: Between May 2020 and February 2022, 27 patients were enrolled. Of these, 24 patients underwent surgery after neoadjuvant treatment (resection rate: 88.9%), and 23 achieved R0 resection (85.2%), meeting the primary endpoint. However, 20 resected patients (83.3%) recurred. Spatiotemporal analysis was performed on matched samples from four R and four NR. In pre-treatment samples from NR group, clusters dominated by fibroblasts (enriched for ECM, EMT, and CAF phenotypes) and B cell subtypes were distinct compared to R group, which exhibited elevated antibody responses and robust T cell and macrophage activity. NR samples showed increased IgM expression but lacked corresponding Fc receptors, suggesting limited immune effector function. Post-treatment NR surgical specimens displayed elevated expression of MUC5AC and CEACAM6 in malignant ductal cells, alongside genes promoting tumor growth. Neoadjuvant mFOLFIRINOX increased fibroblast, while reducing immune cell components. NR tumors formed distinct "resistance niches" after chemotherapy, marked by ECM production, CAF activation, and RTK signaling. Conversely, R tumors showed enhanced epithelial organization with increased type-I hemidesmosome complexes facilitating epithelial adhesion to the basement membrane. Conclusion: Three months of neoadjuvant mFOLFIRINOX was feasible and tolerable for resectable PDAC but associated with high recurrence rate, emphasizing the need for better patient selection. Spatiotemporal analysis revealed critical differences in TME dynamics according to treatment response, including the emergence of resistance niches and distinct pre-treatment spatial signatures. These findings support the integration of spatial biology into future pancreatic cancer trials to improve stratification and therapy. Citation Format: Choong-kun Lee, Changjin Hong, Ho Kyoung Hwang, Min Hwan Kim, Jean Rene Clemenceau, Seock-Jin Chung, Isabel Barnfather, Sumanth Reddy Nakkireddy, Jeong Hwan Park, Ji-Youn Sung, Minji Kim, Yooho Choi, Inyeop Jang, Sunho Park, Sung Hyun Kim, Chang Moo Kang, Hye Jin Choi, Tae Hyun Hwang. Spatiotemporal evolution of the tumor microenvironment predicts treatment response in phase II trial of neoadjuvant chemotherapy for resectable pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 771.

Abstract Abstract 5247 Background: Vena cava filters (VCF) has been used as a method to prevent pulmonary embolism (PE). The indication for VCF in patients with venous thromboembolism (VTE) according to the American College of Chest Physicians (ACCP) guidelines has been changed to recommend that VCF is only indicated in case of contraindication to anticoagulation. Also, there is very limited data describing the long-term effectiveness and safety of these devices if they are not removed. There is no data for VCF in Korea. The aim of this study is to evaluate and compare the change of practice patterns of VCF according to the change of the ACCP guidelines and the outcomes of VCF. Patients and Method: The data from patients who had the placement of VCF from Jan 2001 to Mar 2010 was collected from 6 academic institutes in Korea, retrospectively. We analyzed the patients grouped into 3 groups according to ACCP guidelines published year. These are -2004 group, 2005–2008 group, and 2009- group. Results: All 460 cases were collected and analyzed. Permanent and retrievable filter was 109 (24%) and 351 (76%), respectively. 49% of retrievable filters was attempted to remove and 88% removal success rate was showed. The patient's number is 79 in -2004 group (17%), 254 in 2005–2008 group (55%), and 127 in 2009- group (28%), respectively. The number of patients in indications of VCF was contraindication to anticoagulation 177 (38%), extensive thrombosis for preventing PE 207 (45%), recurrent VTE during anticoagulation 39 (8%), and others 37 (9%), respectively. The practice pattern in indication for VCF was changed in recurrent VTE during anticoagulation (P=0.012). Any complications after VCF insertion were developed in 107/460 (23%) dung follow-up. Inferior vena cava thrombosis, new DVT after placement of VCF, and new DVT with PE after placement of VCF were developed in 45/460 (10%), 91/460 (20%), and 14/460 (3%), respectively. Median follow-up durations were 49.6 months (range, 0–124.4), 12.3 months (0–67.5) and 6.0 months (0–26.9) for -2004, 2005–2008, and 2009- group, respectively. Vena cava thrombosis was significantly decreased in 2009- group (P=0.022). 75% thrombosis-free time was 3.7 months, 13.0 months, and not estimable in -2004, 2005–2008, and 2009- group, respectively (P=0.10). Conclusion: This is first report on VCF in Korea. The practice for indication of VCF insertion in patients with VTE was still out of boundaries from the ACCP guidelines in Korea. Complications after VCF insertion was decreased as time went by. The more follow-up durations was needed to evaluate the development of complication or thrombosis after VCF insertion in 2005–2008 group and 2009- group. Prospective randomized study is needed in Korea to confirm that VCF insertion plus anticoagulation will truly decrease the development of PE than standard anticoagulation. Disclosures: No relevant conflicts of interest to declare.