The remediation of soils and aquifers contaminated by light nonaqueous phase liquid (LNAPL) relies on a precise understanding of the LNAPL distribution above the water table. This study investigates the impact of groundwater table fluctuations and temperature change on LNAPL redistribution in a heterogeneous porous medium through laboratory-scale experiments. Experiments were conducted in a two-dimensional tank simulating aquifer condition, using diesel fuel as the LNAPL. The reservoir, filled with coarse sand and fine sand low-permeability lenses, reproduced the subsurface heterogeneity. Following LNAPL infiltration from the top, controlled drainage and imbibition cycles simulated water table fluctuations. Experiments were conducted at 10 °C and 20 °C to characterize temperature effects. Fluid behavior was monitored using time domain reflectometry (TDR) probes and high-resolution image analysis. Time domain reflectometry measurements provided quantitative dielectric permittivity data, which were converted to saturation profiles. Simultaneously, an image processing approach using the Biodock platform based on AI and OpenCV was used to visualize the spatial distribution of LNAPL, water, and air. Applying the two methods allowed integrated methodology and a detailed understanding of the dynamics driving LNAPL migration. Results show that water table fluctuations significantly affect LNAPL redistribution, with each imbibition cycle leading to LNAPL entrapment in the capillary fringe due to wettability changes and capillary barriers. Higher temperature increased the mobility of LNAPL by reducing its viscosity, resulting in more efficient fluid displacement during drainage. This highlights the importance of studying the fate and transport of pollutants in the laboratory under temperature conditions relevant to aquifers. Low-permeability lenses further modulated LNAPL migration, emphasizing the critical role of subsurface heterogeneity. Overall, the comprehensive experimental design combining TDR and advanced image analysis provides insight into the mechanisms of LNAPL behavior under dynamic environmental conditions and hints at further improvements for predictive models and remediation strategies in contaminated subsurface environments.
e16452 Background: Liver metastasis is a leading cause of death amongst localized pancreatic ductal adenocarcinoma (PDAC) patients following surgical resection. Yet, there are no adjuvant therapies currently available targeting liver colonization in PDAC. We are hindered in our ability to develop such therapies by an incomplete understanding of PDAC liver metastasis' molecular mechanisms. Methods: To address this challenge, we labeled primary mouse PDAC subclones with DNA barcodes to characterize their pre-metastatic state using ATAC-seq and RNA-seq and determine their relative in vivo liver metastasis potential in competition assays in immunocompetent hosts. Results: We identified a gene signature separating metastasis-high and metastasis-low subclones orthogonal to the normal-to-PDAC and classical-to-basal axes. The metastasis-high subclones feature activation of inflammation-related genes and high NF-κB and Zeb/Snail family activity and the metastasis-low subclones feature activation of neuroendocrine, motility, and Wnt pathway genes and high CDX2 and HOXA13 activity. In a functional screen, we validated novel mediators of PDAC liver metastasis related to inflammation, including the NF-κB targets Fos and Il23a , and beyond inflammation including Myo1b and Tmem40 . We scored human PDAC tumors for our signature of metastatic potential from mouse and found that metastases have higher scores than primary tumors. Moreover, primary tumors with higher scores are associated with worse prognosis. We also found that our metastatic potential signature is enriched in other human carcinomas, suggesting that it is conserved across epithelial malignancies. Conclusions: This study establishes a model of clonal evolution during PDAC liver metastasis under immune selective pressure, revealing novel functional regulators amenable to therapeutic intervention in the adjuvant setting. Furthermore, it provides a method for scoring human carcinomas based on metastatic potential that may have prognostic and predictive value across multiple cancer subtypes.
e23555 Background: Synovial sarcoma (SS) is a rare and aggressive form of soft tissue sarcoma which disproportionately affects younger individuals. Optimal treatment for localized disease is unclear. Utilization of perioperative systemic therapy as well as radiation can frequently vary between centers. Here we aim to elucidate associations between multimodality treatment and pt outcomes. Methods: We reviewed 264 pts diagnosed with SS at three sarcoma centers between 2000 and 2024. Demographic data, disease features, and treatment modalities were analyzed by Cox proportional hazard (PH) analysis with the outcomes of OS and DFS. Results: The cohort included 134 males (51%), and 130 females (49%). The most common ethnicities were Caucasian (n = 169, 64%), Hispanic (n = 24, 9%), Asian American and Pacific Islander (n = 34, 13%), and African-American (n = 21, 8%). Median age at diagnosis was 35 yrs (range 6-81 yrs). 56% of the pts had a monophasic SS (n = 150, 56%), deep tumor location with invasion of the fascia (n = 116, 44%), and median tumor diameter of 6 cm (range 1.0-31.0 cm). Tumors arose mostly in the trunk, extremities or chest wall (n = 240, 90%). Neoadjuvant chemotherapy was administered to 100 (38%) pts, with 63 (24%) also receiving neoadjuvant radiation. The most common regimen was Adriamycin-Ifosfamide-Mesna (AIM, n = 87, 33%), with median number of cycles being 3 (range 1-6). External beam radiation therapy (EBRT) was the most common neoadjuvant radiotherapy (n = 59, 22%), and it was administered with chemotherapy in 42 pts (26%). 105 pts (40%) received adjuvant chemotherapy with 48 (17%) also receiving adjuvant radiation. AIM was the most common adjuvant regimen (n = 95, 36%). All pts underwent surgical resection, mostly showing a R0 resection (n = 166, 63%). Multivariate Cox PH analysis showed worse OS for pts with lung nodules ≥ 1 cm at diagnosis (p < 10 -3 ), those with macroscopic residual tumor at the resection margins (p = 0.0002), and pts with larger tumors (p < 10 -3 ). Single-agent neoadjuvant ifosfamide or doxorubicin correlated with worse OS (p = 0.01, p = 0.04), while neoadjuvant EBRT correlated with better OS (p = 0.02). Adjuvant or neoadjuvant combination chemotherapy (AIM) did not correlate with OS (p = 0.76, p = 0.49). Neoadjuvant ifosfamide single-agent (p = 0.002), and larger tumor size (p = 0.0005) correlated with worse DFS. Conclusions: Our findings indicate that tumor size, margin status, and presence of lung nodules at diagnosis are independent risk factors for poor DFS and OS in pts with SS. Neoadjuvant or adjuvant AIM did not improve outcomes and pts receiving single-agent chemotherapy fared worse, suggesting the importance of multi-drug regimens, though our data may suffer from such biases as confounding by indication. These results also indicate that EBRT should be considered for pts with localized SS. Future research is needed to better define outcomes for pts with SS receiving multimodality therapy, prospectively.
11531 Background: Chemotherapy remains the cornerstone for treatment of soft tissue sarcomas (STS). Biomarkers are needed to enhance timely assessment of chemotherapy efficacy to limit toxicity and guide patient management including estimating prognosis and duration of chemotherapy. Methods: This retrospective study includes patients with STS who received chemotherapy in the neoadjuvant or unresectable/metastatic setting at Stanford Sarcoma Center between May 2021 and January 2025. ctDNA was tested with Natera’s CLIA lab using a personalized, tumor-informed ctDNA assay (Signatera, bespoke mPCR, NGS assay). Longitudinal changes in peripheral blood ctDNA were correlated with radiographic response and survival. ctDNA response was defined as > 50% decrease in MTM/mL from baseline, with a second confirmatory measurement. Radiographic response was defined as stable disease or partial response on first re-staging assessment after starting therapy. Overall survival (OS) was defined as time from initiation of chemotherapy to death or last clinical follow up. Progression-free survival (PFS) was defined as time from initiation of chemotherapy to radiographic disease progression, death, or last clinical follow up. Results: Twenty-six patients (median age at diagnosis = 63 years [range 26 – 78]) were included. Histological subtypes consisted of leiomyosarcoma (uterine [n = 10], extrauterine [n = 4]), malignant peripheral nerve sheath tumor (n = 2), undifferentiated pleomorphic sarcoma (n = 2), angiosarcoma (n = 2), and other (Ewing’s sarcoma, malignant phyllodes tumor, perivascular epithelioid cell tumor, low grade myoepithelial carcinoma, high grade uterine sarcoma not otherwise specified, and small round blue cell neoplasm with EWSR1 rearrangement, each n = 1). Chemotherapy consisted of doxorubicin-containing regimens (n = 9), gemcitabine/docetaxel (n = 9), temozolomide-containing regimens (n = 5), and other (cyclophosphamide/topotecan, paclitaxel, and trabectedin, each n = 1). Median follow-up time after initiation of chemotherapy was 12.9 months. 16 of 26 patients had radiographic response. Substantial agreement was observed between ctDNA response and radiographic response (Cohen’s kappa coefficient 0.752). Median OS was longer for ctDNA responders (n = 17) than non-responders (n = 9), at 43.8 months vs 20.6 months (p = 0.03). Median PFS was longer for ctDNA responders than non-responders, at 11.4 months vs 2.0 months (p < 0.001). In the metastatic cohort (n = 22), time on chemotherapy regimen was longer for ctDNA responders than non-responders, median 5.0 vs 2.6 months, p = 0.016 by Wilcoxon rank sum test. Conclusions: Early decline in ctDNA after initiation of chemotherapy correlates with radiographic response and survival in STS. Research is ongoing to evaluate these findings in a prospective study.
