3597 Background: Appendiceal cancer (AC) is a rare malignancy with a distinct immunobiology and propensity for peritoneal metastasis. Tumor-associated macrophages (TAMs) are recognized as influential immune cells in various cancers. In this study, we sought to define the role of TAMs in AC, given its unique immune landscape and peritoneal microenvironment. Methods: Immunohistochemistry-quantified M1-like (CD68+CD86+) and M2-like (CD68+CD206+) TAM densities in 112 archival AC specimens were compared against clinicopathologic features and overall survival (OS). In parallel, a comprehensive tissue proteomic analysis (LC-MS/MS) was performed. Gene set enrichment analysis identified proteomic signatures associated with M1 and M2 density. Independently prognostic proteins were identified via Cox regression. External validation was performed by correlating these proteomic signatures in independent tumor samples from the RIOT-1 clinical trial (NCT05751837), in which AC patients received intra-tumoral lipopolysaccharide (LPS), a TLR4 agonist. Results: M2-like TAMs outnumbered M1-like TAMs in AC (p = 0.0002), particularly in peritoneal metastases (p = 0.002), and were not associated with tumor grade or histology. Low M1 density ( < 18th percentile) correlated with worse OS (HR: 3.26, p = 0.03), while high M2 density ( > 52nd percentile) was associated with improved OS (HR: 0.1, p = 0.03). A combined high-M1/M2 percentile metric was highly prognostic of favorable OS (p < 0.001), independent of age, grade, and disease extent. On proteomic analysis, M1-rich tumors exhibited high bioenergetic demands, extensive metabolic reprogramming (isoprenoid/amino acid metabolism), retinol/xenobiotic metabolism, while M2-rich tumors emphasized ECM remodeling, profound amino acid metabolism (immunosuppressive), oxidoreductase activity, and complement activation, with suppressed cell motility. The combined high-M1/M2 phenotype correlated with intense amino acid/lipid metabolism and redox homeostasis. Five TAM-related, independently prognostic proteins were identified: GATD1 (favorable, HR 1.53x10-16), and AGR2, ENOPH1, RHOA, SERPINB6 (adverse, HRs 5.51-10.39). In RIOT-1, intra-tumoral LPS increased M1/M2 TAM infiltration and induced proteomic changes significantly correlated with M1-related (p = 0.0016), M2-related (p = 0.008), and combined TAM signatures (p = 0.047), supporting therapeutic tractability. Conclusions: AC harbors a TAM-rich immune microenvironment in which M2-like TAMs and a combined M1/M2 phenotype paradoxically associate with favorable prognosis. Distinct TAM-linked metabolic programs and validated prognostic proteins suggest clinically relevant biologic underpinnings of these findings, while modulation of the AC microenvironment via regional innate immune activation may represent a promising therapeutic strategy.

2603 Background: Peritoneal metastases (PM) from gastrointestinal malignancies exhibit immune exclusion and limited responsiveness to systemic immunotherapy. Regional intratumoral immune activation may reprogram the tumor microenvironment (TME). RIOT-1 evaluated the safety, feasibility, and biological effects of intraperitoneal intratumoral lipopolysaccharide (LPS), a Toll-Like Receptor-4 (TLR4) agonist, administered during diagnostic laparoscopy. Methods: RIOT-1 (NCT05751837) was a single-center, open-label Phase I window-of-opportunity trial. Twelve patients with appendiceal or colorectal PM received paired intratumoral injections of 1 µg E. coli O113-derived LPS and normal saline into spatially distinct tumor deposits at laparoscopy, followed by planned cytoreductive surgery 14 days later. The primary endpoint was safety. Secondary endpoints included immune and molecular remodeling assessed by immunohistochemistry (IHC), PhenoCycler multiplex immunofluorescence, spatial neighborhood analysis (CytoMAP), and high-resolution mass-spectrometry proteomics. Key proteomic findings were validated by targeted IHC staining. Results: Intratumoral LPS administration was feasible and well tolerated, with no grade ≥3 adverse events and no interference with subsequent cytoreductive surgery. IHC demonstrated significant post-LPS increases in M1-like macrophages (CD68⁺CD86⁺), M2-like macrophages (CD68⁺CD206⁺), and CD1a⁺ antigen-presenting cells (all p<0.05). PhenoCycler and CytoMAP analyses revealed LPS-specific reorganization of the immune microenvironment, characterized by enrichment of myeloid- and APC-dominant neighborhoods and altered tumor–immune spatial relationships compared with saline-injected controls. Proteomic profiling quantified 5,178 proteins and revealed LPS-specific enrichment of neutrophil degranulation, cytokine-mediated signaling, RNA translation, and autophagy–lysosomal pathways, distinct from biopsy/carrier-associated structural remodeling observed with saline. Upregulated proteins including LYZ, FCER1G, NAIP, and CD68 were confirmed by IHC, supporting localized innate immune activation and metabolic reprogramming. Conclusions: Intraperitoneal intratumoral LPS delivery in PM is safe and biologically active, inducing reproducible innate-dominant immune and metabolic remodeling validated across spatial, proteomic, and histologic platforms. These data establish clinical proof-of-mechanism for regional TLR4 agonism and support further dose-optimization and rational combination strategies in peritoneal malignancies. Clinical trial information: NCT05751837 .

Abstract Background: Peritoneal carcinomatosis (PC) is a late manifestation of abdominopelvic malignancies, often resistant to current treatments due to an incomplete understanding of its biological drivers within the peritoneal immune microenvironment. This study aimed to identify actionable therapeutic targets for PC by analyzing peritoneal soluble mediators and cellular composition in patients. Building on existing evidence implicating IL-8 as a critical mediator of tumor-associated inflammation and immunosuppression in other cancers and preliminary data in PC, the study also evaluated IL-8 pathway inhibition in a preclinical model. Methods: Peritoneal tissue and fluid were collected from three patient groups: patients without benign conditions (n=15), cancer without PC (n=30), and confirmed PC (n=41). Immunohistochemistry was used to quantify immune cells in tissue and Luminex panels to analyze immune, inflammatory, and growth factors in peritoneal fluid. Statistical analyses identified group differences, correlations with disease burden (Peritoneal Cancer Index - PCI), and overall survival (OS). To assess therapeutic tractability of IL-8 axis blockade, a bioluminescent CT26-luc murine PC model was treated daily with the CXCR2 antagonist AZD5069 (100 mg/kg) or saline from day 0-9, with serial IVIS imaging, body-weight monitoring, and survival tracking through day 11. Results: PC tissue exhibited increased immune cell infiltration compared to non-PC groups, including elevated mast cells, neutrophils, CD4+ T cells, CD14+ monocytes, CD20+ B cells, and CD138+ plasma cells. Secretomic analysis of peritoneal fluid in PC revealed a dominant IL-6/IL-8-centered inflammatory signature, with increased GRO, IL-6, IL-8, CXCL10, IL-10, and TGF-β. This pattern supports pro-angiogenic, immunosuppressive, and stromal-activation signaling. Densities of CD4+, CD14+, CD20+, and CD138+ cells positively correlated with PCI, indicating progressive immune-stromal co-evolution with tumor burden. In human samples, neutrophil infiltration correlated with worse OS, while CD1a+ dendritic cell enrichment correlated with improved OS, underscoring the clinical relevance of the immunologic findings. In the murine model, AZD5069 demonstrated a therapeutic effect in 4 of 10 treated mice, suggesting potential efficacy of IL-8-axis targeting in specific patient subsets. Conclusion: PC is characterized by distinct immune cell infiltration and a significant IL-6/IL-8 cytokine network. Both neutrophil infiltration and the IL-6/IL-8 axis are associated with disease burden and patient survival, highlighting the IL-6/IL-8 axis as a relevant therapeutic target. Preclinical evidence supports its potential in specific patient groups. Further research is needed to identify predictive biomarkers for treatment response and translate these findings into clinical strategies. Citation Format: Christopher Sherry, Neda Dadgar, Zuqiang Liu, Yong Fan, Hyun Young Park, Ali Zaidi, Paige Mirsky, Oleksii Kucherenko, Albert Donnenberg, David L. Bartlett, Vera S. Donnenberg, Patrick Wagner. Integrated tissue and secretome profiling identifies an IL-6/IL-8-dominant immune phenotype in peritoneal carcinomatosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7952.

Peritoneal carcinomatosis occurs when the parietal and visceral peritoneum are involved with multifocal metastatic tumors, most commonly arising from abdominopelvic organ sites. The prevailing model of peritoneal carcinomatosis sees the peritoneal lining as the ‘soil’ onto which metastatic cancer cells attach and grow. Molecular methods to assess the functional status of this microenvironment have not been well developed. To address this gap, we analyzed the protein composition of peritoneal tissue using liquid chromatography-tandem mass spectrometry on both fresh frozen and formalin-fixed, paraffin-embedded benign tissue (FFPE) samples, employing an ultra-high-resolution timsTOF mass spectrometer. The protein yield in peritoneal tissue was lower than that observed from similar studies of other visceral organ tissues. Extracellular matrix (ECM) proteins were present in high abundance and may be contributory to cancer cell attachment and invasion in peritoneal carcinomatosis. We further quantified key signal transduction and metabolic proteins known to contribute to cancer progression, along with defined tumor suppressors and oncoproteins. Our findings represent a baseline catalog of the proteomic composition of the peritoneal lining, as a comparison dataset for future studies focused on alterations in pathologic states such as peritoneal carcinomatosis.

Peritoneal carcinomatosis (PC) and malignant pleural effusions (MPE) are two common complications of cancers metastatic to the respective body cavities. A PC diagnosis indicates metastasis to the tissue lining the abdominal cavity and is most common in patients with gastrointestinal and gynecological cancers. It is often accompanied by ascites, an accumulation of serous fluid in the abdomen. MPE presents as the accumulation of fluid in the space between the lungs and chest wall. It is a common terminal event in patients diagnosed with breast cancer, lung cancer, lymphoma, and mesothelial cancers, and less commonly, in a wide variety of other epithelial cancers. Due to the aggressive nature of cavitary tumors, the outcome of current treatments for both PC and MPE remains bleak. Although PC and MPE are characteristically affected by different sets of primary tumors (lung/breast/mesothelioma for MPE and gynecologic/gastrointestinal for PC), their environments share common cytokines and cellular components. Owing to the unique cytokine and chemokine content, this environment promotes aggressive tumor behavior and paradoxically both recruits and suppresses central memory and effector memory T cells. The cellular and secretomic complexity of the cavitary tumor environment renders most currently available therapeutics ineffective but also invites approaches that leverage the robust T-cell infiltrate while addressing the causes of local suppression of anti-tumor immunity. Interactions between the heterogeneous components of the tumor environment are an area of active research. We highlight the roles of the immune cell infiltrate, stromal cells, and tumor cells, and the soluble products that they secrete into their environment. A more comprehensive understanding of the cavitary tumor environment can be expected to lead to better immunotherapeutic approaches to these devastating conditions.

Peritoneal carcinomatosis (PC) is a late-stage manifestation of abdominopelvic malignancies with poor prognosis and limited treatment options. Unique biochemical mechanisms within the peritoneal cavity play a key role in disease progression and resistance to therapy. Despite current therapies like systemic chemotherapy and cytoreductive surgery, patients frequently develop severe complications, including bowel obstruction, nutritional decline, and ascites, driving the need to address the pro-tumorigenic niche in the peritoneal cavity. The immune microenvironment in PC is marked by elevated proinflammatory mediators, such as IL-6 and IL-8, which skew the response toward innate rather than adaptive immune responses. IL-8 signaling, through its receptors CXCR1 and CXCR2, promotes neutrophil recruitment, chronic inflammation, angiogenesis, epithelial–mesenchymal transition, and immune evasion, making the IL-8/CXCR1/CXCR2 axis a potential therapeutic target in PC. Pre-clinical models provide evidence that IL-8 or CXCR1/CXCR2 blockade may be a valuable therapeutic strategy. IL-8 targeting agents such as monoclonal antibodies (BMS-986253) and small-molecule inhibitors (SX-682, AZD5069, navarixin) have shown efficacy in mitigating tumor growth and improving the efficacy of immune checkpoint inhibitors. Phase I and II trials have demonstrated encouraging safety profiles and preliminary efficacy when treating multiple abdominopelvic malignancies. In this review, we discuss the influence of the IL-8/CXCR1/CXCR2 axis within the peritoneal immune environment in PC and highlight recent work using IL-8 or CXCR1/CXCR2 blockade as a therapeutic strategy for PC. Continued research into the peritoneal immune microenvironment and the development of targeted therapies are essential for improving the management and prognosis of PC, potentially enhancing antitumor immunity and patient outcomes.

Emerging evidence highlights the role of the tumor microbiome, including Fusobacterium nucleatum (Fn), in a wide range of gastrointestinal cancers. Fn purportedly contributes to tumorigenesis by activating oncogenic pathways and modulating immune responses. Although the prevalence and impact of Fn has been extensively studied in colorectal cancer, no previous systematic or in situ studies have been performed in appendiceal cancer (AC). The aim of this study was to evaluate the prevalence and association of Fn density in AC with clinical factors and oncologic outcomes. Archival tissue from 54 patients with AC was assessed for Fn density using RNA in situ hybridization. Clinicopathological variables were obtained for each case through electronic medical record review, and the immune microenvironment was characterized in each case using immunohistochemistry to quantify CD3+ and CD8+ T lymphocytes and M1-/M2-like tumor-associated macrophages. In AC, Fn density was associated with patient age, tumor grade, and histologic subtype. Fn was negatively associated with CD3+ and CD8+ T lymphocytes and positively associated with M2-like TAMs in low-grade AC. Interestingly, tumor Fn content was associated with better overall and progression-free survival, even when controlling for tumor grade. In this exploratory study, we found that Fn is prevalent in AC. Fn is associated with a number of clinical, pathologic, immunologic, and prognostic variables in AC that are distinct from the corresponding observed associations in colorectal cancer. Further research is warranted to validate these findings and explore the mechanistic contributions of Fn to AC pathogenesis or immune response.

Breast cancer (BC) metastatic to the pleura is uniformly fatal with a median survival of six months and quality of life that is diminished by dyspnea, pain and discomfort. There are currently no curative treatments once malignant pleural effusions (MPE) have occurred. Despite significant clinical progress in immuno-oncology, there has been almost no change in survival or quality of life for patients with MPE. We have shown that BC MPE are characterized by a distinct and complex pleural secretome that varies little between breast cancer subtypes. Our studies on freshly isolated pleural T cells (PIT) from breast cancer MPE of all subtypes indicate that these cells are quiescent rather than exhausted, and poised to mount potent anti-autologous tumor effector responses, but locally suppressed by the pleural environment. To date, there are no reports on cytokine secretion and immune checkpoint expression in pleural T cells isolated from patients with invasive lobular carcinoma (ILC) metastatic to the pleura. In this abstract we show that freshly isolated pleural T cells from patients with ILC secrete T-cell effector cytokines (IL-2 or IFNγ), are not exhausted (lack or have low expression of PD1, TIM3, LAG3, TIGIT, CTLA4) and a minority express CD137/4-1BB activation/signal transduction molecule, critical to anti-tumor effectors. Consistent with our findings in BC grouped by HR status, the 8 most prevalent cytokines in the pleural secretome (CXCL10, CCL2, sIL-6Rα, IL-6, CXCL1, TGFβ, CCL11, IL-10) are indistinguishable between ILC and IDC. However, ILC cases clustered together in hierarchical clustering across 40 measured cytokines, due chiefly to a paucity of G-CSF, VEGF, IL-7, and an excess of IL-4. The data suggest that ILC PIT are immunologically competent when removed from their suppressive environment and can be used to generate an adoptive cellular therapeutic. Citation Format: Vera Donnenberg, Albert Donnenberg, James Luketich, Shannon Puhalla, Christie Hilton, David Bartlett. PLEURAL T CELLS FROM PATIENTS WITH METASTATIC INVASIVE LOBULAR CARCINOMA PRODUCE EFFECTOR CYTOKINES AND MOUNT ANTI-TUMOR IMMUNITY [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-09-24.

BACKGROUND OR PURPOSE:Carcinomatosis, a distinct pattern of metastatic cancer in the peritoneal cavity, poses challenges for treatment and has limited therapeutic options. Understanding the immune environment of peritoneal surface malignancies is crucial for developing effective immunotherapeutic approaches. This study characterizes soluble immune mediators in the peritoneal fluid of patients with and without carcinomatosis to identify targets for novel treatment strategies.PATIENTS AND METHODS:Serum and peritoneal fluid samples were collected from surgical patients, and a multianalyte analysis was performed using the Luminex platform. Patient characteristics, tumor sites, and sample collection details were recorded. Soluble immune mediator levels were measured and compared between peritoneal fluid and serum samples and among clinical subgroups. Statistical analysis was conducted to assess differences in analyte concentrations and correlations between samples.RESULTS:There were 39 patients included in the study, with varying surgical indications. Significant differences were observed in soluble immune mediator levels between peritoneal fluid and serum, with peritoneal fluid exhibiting lower concentrations. Carcinomatosis was associated with elevated levels of proinflammatory mediators, including IL-6 and IL-8, while adaptive immune response markers were low in peritoneal fluid.CONCLUSIONS:The peritoneal immune microenvironment in carcinomatosis favors innate immunity, presenting a challenging environment for effective antitumor response. High levels of proinflammatory mediators suggest potential targets for intervention, such as the IL-6 axis, FGF2, IL-8, and CCL2; these could be explored as potential mitigators of malignant ascites and enhance anti-tumor immune responses. These findings provide valuable insights for developing immunotherapy strategies and improving outcomes in patients with peritoneal carcinomatosis.

BACKGROUND AIMS:Cancers of many different tissue origins can metastasize to the pleura, a space with a unique immune environment that predisposes to aggressive tumor behavior and the development of effusions, an exudative leakage of serous fluid accompanied by an immune infiltrate. Effusions are drained therapeutically to relieve dyspnea, often several times per week. Characteristically, they contain 50-1000 × 106 viable pleural T cells (PITs), which can be reliably activated and expanded in culture, making them an ideal source for generation of a cellular therapeutic. We sought to determine the feasibility of a Good Manufacturing Practice-compliant, rapidly manufactured adoptive cellular therapeutic from pleural-infiltrating T cells and to determine the cytolytic activity against autologous tumor, cytokine secretion profile, and immune check point molecule (ICM) expression. METHODS:Six products were generated from consecutively collected malignant pleural effusions (MPEs) drained from patients with breast (4) or non-small cell lung (2) cancer metastatic to the pleura. CD4+ and CD8+ cells were immunomagnetically selected, stimulated with anti-CD3/anti-CD28 and expanded in the presence of interleukin (IL)-7 and IL-15 (12.5 ng/mL each) using the Miltenyi CliniMACS Prodigy device. Cells were cultured for 8- 12 days. Cytokines were assayed in the MPE and in the culture medium before harvest using a multiplexed bead assay. Cytolytic activity of the final cellular product formulation against an autologous tumor was measured in a 4-hour killing assay by lactate dehydrogenase release. T-cell content, ICM expression and intracellular interferon ɣ were assessed by flow cytometry. RESULTS:All MPEs successfully generated products containing 0.7 to 3.2 × 109 viable T cells. All final products showed no growth in bacterial or fungal cultures. T-cell purity was 98.3 ± 1.7% (mean, standard deviation), viability was 97.6 ± 1.7% and T-cell fold expansion was 14.3 ± 10.6. Twenty cytokines (excluding IL-7 and IL-15) were present in the culture supernatants at ≥10 pmol/L. These include granzyme B, interferon-ɣ, IL-13, perforin, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α. In the final cellular product formulation, 69 ± 28% of CD4+ T cells, and 75 ± 27% of CD8+ T-cells produced interferon-ɣ without additional stimulation. ICM expression was well correlated between CD4+ and CD8+ T cells and was relatively low, with TIGIT (44.6 ± 10.9%) and programmed cell death protein 1(21.1 ± 6.7%) being the highest. All products evidenced cytolytic activity against an autologous tumor, with maximal lysis ranging from 19.4% to 100% and cytolytic indices ranging from 4.3 to 21.1. CONCLUSIONS:We conclude that Fast tumor-infiltrating lymphocytes (Fast TIL), an adoptive cellular therapeutic generated from drained MPEs, can be rapidly and reliably manufactured using the Prodigy system. The products have demonstrable in vitro effector activity against an autologous tumor. Expression of interferon-ɣ in the majority of cells, without accompanying elevated expression of ICM, suggests that the cells have not been exhausted during expansion. Based in part on the results presented here, the US Food and Drug Administration has issued Investigational New Drug status (IND # 30892) for the rapid manufacture of PIT-based cellular therapeutic (Fast TIL), paving the way for a first-in-human clinical trial (supported by CDMRP-TTSA CA230972). We plan to infuse this product intrapleurally, accompanied by low-dose intrapleural IL-2 with the expectation that infused cells will immediately encounter tumor antigens, continue to expand in the pleural space, and migrate to the peripheral circulation.

BackgroundMany cancers metastasize to the pleura, resulting in effusions that cause dyspnea and discomfort. Regardless of the tissue of origin, pleural malignancies are aggressive and uniformly fatal, with no treatment shown to prolong life. The pleural mesothelial monolayer is joined by tight junctions forming a contained bioreactor-like space, concentrating cytokines and chemokines secreted by the mesothelium, tumor, and infiltrating immune cells. This space represents a unique environment that profoundly influences tumor and immune cell behavior. Defining the pleural secretome is an important step in the rational development localized intrapleural immunotherapy.MethodWe measured cytokine/chemokine content of 252 malignant pleural effusion (MPE) samples across multiple cancers using a 40-analyte panel and Luminex multiplexing technology.ResultsEleven analytes were consistently present in concentrations ≥ 10.0 pM: CXCL10/IP10 (geometric mean = 672.3 pM), CCL2/MCP1 (562.9 pM), sIL-6Rα (403.1 pM), IL-6 (137.6 pM), CXCL1/GRO (80.3 pM), TGFβ1 (76.8 pM), CCL22/MDC (54.8 pM), CXCL8/IL-8 (29.2 pM), CCL11/Eotaxin (12.6 pM), IL-10 (11.3 pM), and G-CSF (11.0 pM). All are capable of mediating chemotaxis, promotion of epithelial to mesenchymal transition, or immunosuppression, and many of are reportedly downstream of a pro-inflammatory cytokine cascade mediated by cytokine IL-6 and its soluble receptor.ConclusionThe data indicate high concentrations of several cytokines and chemokines across epithelial cancers metastatic to the pleura and support the contention that the pleural environment is the major factor responsible for the clinical course of MPE across cancer types. A sIL-6Rα to IL-6 molar ratio of 2.7 ensures that virtually all epithelial, immune and vascular endothelial cells in the pleural environment are affected by IL-6 signaling. The central role likely played by IL-6 in the pathogenesis of MPE argues in favor of a therapeutic approach targeting the IL-6/IL-6R axis.

BackgroundIntra-tumoral immunotherapy has shown potential in treating advanced cancers. Delivery challenges have limited exploration of these modalities in intra-abdominal tumors. In this study, we explore the safety of injecting intra-abdominal tumors with lipopolysaccharide (LPS) from Escherichia coli 0113. This agonist of toll-like receptor 4 (TLR4) holds promise as an agent to enhance the anti-tumor immune response within the tumor microenvironment.MethodsThis Phase I study will recruit adult patients with peritoneal metastases from gastrointestinal primary malignancies who have at least two suitable intra-abdominal soft tissue tumors for injection. LPS will be administered as a single 1μg dose during diagnostic laparoscopy in patients in whom a subsequent interval laparotomy is planned. A control injection of saline will be injected into a second lesion. Primary outcome is safety, with secondary outcomes being biomarkers of the tumor immune microenvironment in pre- and post-treatment biopsies.ResultsThe primary endpoint is to determine the safety (frequency and nature of adverse events) following intra-tumoral LPS injection. Adverse events will be classified using Common Terminology Criteria for Adverse Events. Secondary endpoints include cellular and molecular biomarkers of immune response. The study will proceed until twelve patients have completed the protocol.DiscussionPatients undergoing standard-of-care laparoscopy in preparation for interval cytoreductive surgery may be ideal candidates for intra-tumoral immunotherapy. This study seeks to establish the safety of using E. coli LPS for injection into intra-abdominal tumors and to establish precedent for interval tumor immune microenvironment assessment as a window-of-opportunity concept in the context of abdominal metastatic disease.Trial RegistrationThe trial is registered at Clinical Trials.gov; NCT05751837 (registered February 28th, 2023).