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PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE. CONCLUSION This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.

Abstract Malignant insulinomas are rare pancreatic neuroendocrine tumors characterized by excessive insulin secretion and a high propensity for metastasis, leading to challenging management. This study retrospectively analyzed 57 patients treated for malignant insulinoma at Mayo Clinic sites between 1992 and 2024, focusing on the efficacy of systemic therapies in improving hypoglycemic control and survival outcomes. The most commonly used therapies included somatostatin analogs (SSA), everolimus, capecitabine-temozolomide (CAPTEM), and peptide receptor radionuclide therapy (PRRT). PRRT demonstrated the highest efficacy in controlling hypoglycemia (93%), followed by CAPTEM (68%) and everolimus (62%). SSA, chemotherapy, and streptozocin were less effective, with hypoglycemic improvement seen in 37.5, 33.3, and 28.6% of patients, respectively. Overall survival (OS) was longest with SSA at 84.67 months, followed by CAPTEM at 81.67 months and everolimus at 74.07 months. PRRT demonstrated a median OS of 49.73 months. In contrast, chemotherapy and streptozocin-based therapies had significantly shorter OS times of 15.23 and 8.35 months, respectively. These findings highlight significant variability in systemic therapy efficacy for malignant insulinoma, with PRRT emerging as a promising treatment for refractory hypoglycemia and long survival. Cox regression analysis identified primary tumor resection and a history of benign insulinoma as associated with longer OS. Optimal sequencing of therapies remains unclear, and individualized treatment plans based on hypoglycemic burden and tumor characteristics are critical for improving survival and quality of life in these patients.

10051 Background: CBL0137 is a novel agent that targets the FAcilitates Chromatin Transcription complex (FACT), a histone chaperone that regulates chromatin remodeling during transcription, replication, and DNA repair. CBL0137 has been shown to have anti-tumor activity in multiple preclinical models of pediatric cancer. We report the phase 1 trial of CBL0137 in children with relapsed or refractory solid tumors including central nervous system (CNS) tumors or lymphoma (NCT04870944). Methods: Patients (age 12 months to 21 years) with relapsed/refractory solid tumors, central nervous system tumors or lymphoma were eligible. In the dose escalation phase, a rolling-six design was used to evaluate CBL0137 administered intravenously (IV) once per week on Days 1 and 8 of a 21-day cycle. The starting dose was 400 mg/m 2 , with escalation to the adult phase 2 dose (RP2D) of 540 mg/m 2 . The maximum tolerated dose (MTD) was determined based on cycle 1 dose limiting toxicity (DLT) using Common Toxicity Criteria for Adverse Events (v5). Pharmacokinetics (PK) and cytokine analyses were performed during cycle 1. Seven additional patients ( < 18 years old) were accrued to a PK expansion cohort at the RP2D. Results: Sixteen patients were enrolled; 14 were evaluable for DLT assessment (12 at 400mg/m 2 [6 in dose escalation and 6 in PK expansion] and 2 at 540mg/m 2 ). The median (range) age was 10 (4-20) years. Diagnoses included high grade glioma (n = 6), osteosarcoma (n = 5), ependymoma (n = 2), neuroblastoma, hepatoblastoma and Burkitt’s lymphoma (1 each). One of 12 evaluable patients treated at 400 mg/m 2 experienced a DLT: Grade 3 photosensitivity. At 540 mg/m 2 , the two evaluable patients both had fever and dose limiting Grade 3 hypotension. Non-dose limiting Grade 3-4 toxicities included anemia, lymphopenia, neutropenia, thrombocytopenia, hypokalemia, anorexia, photosensitivity and fever. For both dose levels, a total of 12 patients were reported to have at least one episode of Grades 1-3 fever and/or Grade 1 cytokine release syndrome (CRS). PK parameters (mean±SD) for CBL0137 (400 mg/m 2 ) were T max = 0.7 ± 0.5 h, C max = 1310 ± 417 ng/mL, and AUC 0-24h = 15300 ± 6790 h·ng/mL. Given the unexpected toxicities of fever, hypotension, and CRS, cytokine samples were collected in patients enrolled in the PK expansion cohort; all had Grade 1 CRS and significantly elevated levels of both IL-10 (adj p = 0.001) and IL-1RA (adj p < 0.001) at 24 hours vs pre-infusion. Conclusions: The RP2D and MTD of CBL0137 in children and adolescents with solid or CNS tumors is 400mg/m 2 IV weekly on Days 1 and 8 of 21-day cycles. CBL0137 leads to immune activation, with cytokine elevation and the possibility of CRS, an unexpected toxicity not previously reported in adults. A Phase 2 cohort in patients with Diffuse Midline Glioma is ongoing and includes further assessment of immune activation. Clinical trial information: NCT04870944 .

8644 Background: RET fusions are targetable oncogenic drivers in 1-2% of non-small cell lung cancers (NSCLC). ARROW (NCT03037385) study results (final data lock May 20, 2024) supported the US FDA approval of pralsetinib, a highly potent, oral, selective RET inhibitor for metastatic RET -altered NSCLC. Here, we present final study results. Methods: ARROW was a phase 1/2 open-label study conducted at 84 sites in 13 countries. Phase 2 included patients with RET -fusion-positive NSCLC who received 400 mg pralsetinib once daily (QD). Initially, treatment-naïve patients were not candidates for platinum-based therapy and presented with several unfavorable prognostic factors; this requirement was removed by protocol amendment in July 2019. Primary objectives were overall response rate (ORR, per RECIST v1.1) and safety. Progression-free survival (PFS) and overall survival (OS) are reported in the full efficacy population; the measurable disease population (MDP) was the primary analysis population for ORR and duration of response (DOR). Results: 281 patients with RET -fusion-positive NSCLC received pralsetinib 400 mg QD, with a median duration of treatment of 14.95 months (mos). Median age was 60 years; 46% were male. In the MDP (n=259), ORR was 70.3% (95% confidence intervals [CI]: 64.3, 75.8) and median DOR was 19.1 mos (95% CI: 14.5, 27.9; Table). In the efficacy population (N=281), median OS was 44.3 mos (95% CI: 30.9, 53.1) with median follow up of 47.6 mos (95% CI: 44.8, 49.2), and median PFS was 13.1 mos (95% CI: 11.4, 16.8). ORR (Table) and median PFS were markedly higher in the US (25.9 mos, n=64) vs. Asia (12.6 mos, n=122) or Europe (12.9 mos, n=95). In the safety population, 95% of patients experienced treatment-related adverse events (TRAEs); 66% experienced ≥grade 3. Common TRAEs included increased AST (n=128 [46%]), anemia (n=121 [43%]), increased ALT (n=98 [35%]), and hypertension (n=77 [27%]). 3 patients died due to TRAEs (pneumonia, n=2; interstitial lung disease and rhabdomyolysis, n=1 each). No new safety signals were identified with this update. Conclusions: Pralsetinib produced clinically meaningful and durable responses in patients with RET -fusion-positive NSCLC (regardless of prior therapies) with a manageable safety profile, confirming with this longer follow up previously published results. Clinical trial information: NCT03037385 . All MDP(n=259) Prior Platinum (n=130) Treatment-naive(n=106) ORR, % (95% CI) Overall 70.3(64.3, 75.8) 63.1(54.2, 71.4) 78.3(69.2, 85.7) US (n=58)77.6(64.7, 87.5) (n=31)64.5(45.4, 80.8) (n=19)100(82.4, 100) Europe (n=89)65.2(54.3, 75) (n=36)63.9(46.2, 79.2) (n=43)65.1(49.1, 79) Asia (n=112)70.5(61.2, 78.8) (n=63)61.9(48.8, 73.9) (n=44)81.8(67.3, 91.8) Median DOR, mos (95% CI) a (n=182)19.1(14.5, 27.9) (n=82)31.8(15.1, 40.4) (n=83)13.4(9.4, 21.7) Median DOR follow up, mos (95% CI) 46.8(42.3, 50.2) 50.3(46.9, 56.8) 42.3(37.4, 44.2) a Per FDA censoring rule.

TPS9607 Background: The majority of 100,000 annual new U.S. cases of mel consist of localized early-stage disease that undergo wide local excision (WLE) +/- SLN biopsy (SLNB). The tumor draining lymph node is the initial site of immune response including formation of tumor mediated immune suppression and pre-metastatic niches. SLN positivity is a key prognostic factor in early stage mel. Thus, the SLN is a target for local immune intervention to boost the antitumor response. Vusolimogene oderparepvec (RP1) is an intratumorally administered oncolytic immunotherapy with unique potential for neo-adjuvant therapeutic application. RP1 is constructed from a high potency HSV1 strain (RH018A) modified to replicate selectively in tumors (deletion of neurovirulence factors ICP34.5 and ICP47). RP1 encodes GM-CSF and a fusogenic GALV-GP R- protein to maximize oncolytic potency and induce immunogenic cell death. Preclinical and clinical data demonstrate robust antitumor efficacy (including non-injected lesions) of RP1 alone and in combination with checkpoint inhibitors in advanced mel. This trial addresses a crucial gap in understanding the impact of RP1 on SLN dynamics and preventing disease recurrence in high-risk patients (pts). We hypothesize that in pts with high risk, clinically node negative mel (pT3b-T4b), RP1 will reduce rates of SLN positivity as compared to a historic control by favorably reshaping the immune landscape of the primary tumor, SLN, and the peripheral blood. Methods: This is an investigator-initiated, single arm phase 1/2 trial (NCT06216938) designed to assess efficacy and safety of neo-adjuvant RP1 in high-risk, clinically node-negative, non-uveal mel. Eligibility criteria: pT3b, T4a, or T4b non-uveal mel with visible residual tumor or positive biopsy margins, ECOG ≤1, and no prior oncolytic virus therapy. Pts receive 3 doses of neo-adjuvant RP1 (10e6 PFU day 1, 10e7 PFU on days 15 and 21), injected at the primary tumor site followed by standard WLE and SLNB within 35 days of dose 1. Biopsy of residual tumor or archival tumor tissue is obtained pre-RP1 and archival tissue from WLE and SLNB is obtained post-RP1. Blood samples are obtained with each RP1 dose and 3 months post-therapy. Pts are followed for 3 years. Primary endpoint: rate of SLN positivity in the overall cohort. Secondary endpoints: treatment related adverse events (per CTCAE), recurrence free survival, and overall survival. Exploratory endpoints: immunophenotype and microenvironment of the primary tumor, SLN and peripheral blood pre- and post- RP1 (via IHC, IF, and flow cytometry). The observed rate of SLN positivity will be compared to the predicted rate (Melanoma Institute of Australia Prediction Tool for SLN metastatic risk) with a one-sided, one-sample proportion test. Kaplan-Meier estimates will be provided for survival endpoints. The trial is active with 13 of 25 pts enrolled in January 2025. Clinical trial information: NCT06216938 .

e16330 Background: Sarcomatoid hepatocellular carcinoma (SHC) is a rare and aggressive variant of hepatocellular carcinoma (HCC), accounting for less than 2% of all primary liver cancers. Characterized by the presence of both epithelial and mesenchymal components, SHC demonstrates a high degree of cellular plasticity, often associated with epithelial-mesenchymal transition. This phenotypic heterogeneity contributes to its aggressive clinical behavior, including rapid tumor progression, early metastasis, and poor response to conventional therapies. As a result, patients diagnosed with SHC typically have a median survival of less than 12 months, significantly lower than that observed in patients with conventional HCC. Methods: We conducted a retrospective study at the Mayo Clinic Comprehensive Cancer Center, focusing on patients diagnosed with SHC between April 2017 and December 2023. The data collected included demographics, performance status, underlying risk factors, alpha-fetoprotein (AFP) levels, next generation sequencing (NGS) testing, and the treatment received. Results: A total of ten patients with confirmed diagnoses of SHC were included, with median age at the time of diagnosis 63.5 years (37-77), predimonantly male (9 out of 10), and identifying white (8 out of 10). Alcoholic cirrhosis was identified as an underlying risk factor in three patients, NASH cirrhosis in two, and HCV in two patients. The majority (6 out of 10) of the patients had localized disease, with 4 patients having denovo metastatic disease with abdominal lymph node involvement. Five patients had NGS testing (Tempus, Guardant 360, and ProvsSeq523), with resultant pathogenic variants including TP53 in 3 patients, NTRK3 fusion, IDH2, EGFR, TERT, MLH1, ARIS1A, and PALB2. Four patients were treated with combined Yitrrium-90 and systemic therapy. Three patient started systemic therapy, and two patients underwent surgical resection. Systemic Therapy used included combined Atezolizumab/ Bevacizuamab, Pembrolizumab/ Lenvatinib, Gemcitabine/ Docetaxel, Gemcitabine/ Cisplatin, Cabozantinib, and pembrolizumab monotherapy. The median overall survival for this group was 11.5 months; 95% confidence interval (CI): 4.66-40.1 months. Seventy percent experienced progression, with a median progression-free survival after first line of treatment of 2.5 months; 95% CI: 1-15.3 months. Conclusions: Sarcomatoid HCC remains aggressive and difficult to treat cancer with limited overall survival. Immunotherapy based regimens have limited efficacy for this HCC variant.

e16265 Background: The pivotal TOPAZ-1 trial established durvalumab plus gemcitabine and cisplatin (GC) as a new first-line standard of care for advanced biliary tract cancer (ABTC). However, weekly administration of GC can lead to significant toxicity limiting its tolerability in clinical practice. Based on previous studies, we implemented biweekly regimen of GC on days 1 and 15 together with durvalumab on day 1 of each 28-day cycle to optimize the treatment delivery and improve tolerability. Here, we report the Mayo Clinic experience with biweekly GC with monthly durvalumab in patients with ABTC. Methods: At our three-site institution, we retrospectively identified patients with ABTC between January 2021 and August 2024, who received biweekly GC with monthly durvalumab. Patient demographics, tumor characteristics, treatment details - treatment related adverse events (trAEs) graded according to the NCTCAE V5.0 were collected. Outcomes included median progression-free survival (mPFS), median overall survival (mOS) and clinically assessed overall response rate (ORR) and disease control rate (DCR). Results: 57 patients were included in our analysis, median age was 68 years (range 35-90), and 57.9% were females. 91.2% of patients had ECOG performance status of 0-1. 71.9% had intrahepatic cholangiocarcinoma, 19.3% extrahepatic cholangiocarcinoma and 8.7% gallbladder carcinoma. 70.2% had metastatic disease, 21 % locally advanced unresectable disease and 8.7% recurrent metastatic disease. Patients were followed for a median of 9.1 months (2.3-28.5). 91.2% of the patients received biweekly GC plus monthly durvalumab while 8.8% switched from weekly to biweekly GC plus monthly durvalumab due to treatment toxicities. Median number of treatment cycles was 5. Maintenance regimens included durvalumab (19.3%), gemcitabine/durvalumab (8.8%) and GC/durvalumab (8.8%). Median duration of follow up was 9.1 months (range 2.3 – 28.5). ORR was 36.9% and DCR was 72% (complete response 5.3%, partial response 31.6% and stable disease 35.1%). mPFS was 7.2 months, while mOS was 16 months. Grade(G) 3 or 4 trAEs included abnormal liver function tests (15.7%), infections (11.5%), anemia (8.7%), thrombocytopenia (5.2%), peripheral neuropathy (1.7%), acute kidney injury (1.7%). Immune-related AEs were noted in 6 patients (10.5%) including colitis, gastritis, hepatitis, myocarditis and hypothyroidism. There was no patient with severe neutropenia or febrile neutropenia. Only 5 patients (8.8%) stopped treatment due to trAEs. Conclusions: Biweekly GC on days 1 and 15 plus durvalumab on day 1 of each 28-day cycle is associated with a more favorable toxicity profile while maintaining efficacy similar to that observed in the TOPAZ-1 trial indicating that a de-escalation strategy is feasible with improvement in patient centered outcomes.

e16157 Background: The optimal treatment for resectable gastric/GEJ AC is unclear due to limited direct comparisons among chemotherapy and chemoradiation regimens. Addressing this gap is critical to improve patient outcomes. We performed this network meta-analysis (NMA) to determine the relative efficacy of multimodality regimens for resectable gastric/GEJ AC. Methods: MEDLINE, EMBASE, Scopus, and CENTRAL were searched from inception till September 20, 2024, to identify phase III trials evaluating perioperative/neoadjuvant systemic therapy ± radiation in resectable gastric/GEJ AC. Primary outcomes were disease-free survival (DFS) and overall survival (OS). A frequentist NMA was conducted to compare hazard ratios (HR) and 95% CI for each outcome. Relative treatment rankings were assessed using P-scores. Results: Fifteen trials (8,072 patients) were analyzed. pFLOT (perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel) ranked highest for DFS in the overall population (P score 91%) (Table), significantly outperforming surgery alone (HR 0.48, 95% CI 0.38-0.60) and nCROSS (neoadjuvant paclitaxel, carboplatin and radiotherapy) (0.67, 0.56-0.81). For OS, nPLF+nCRT(EP) (neoadjuvant cisplatin, leucovorin and fluorouracil for induction, followed by etoposide, cisplatin, and radiotherapy) (P score 90%) and pFLOT (P score 87%) were the top regimens, with pFLOT significantly outperforming surgery alone (0.57, 0.45-0.72), and nCROSS (0.73, 0.60-0.89). Adding neoadjuvant chemoradiation to pFLOT provided no additional OS (1.14, 0.76-1.72) or DFS (1.22, 0.83-1.82) benefit. Similarly, adding pembrolizumab to perioperative chemotherapy (CF/CX) (cisplatin and fluorouracil/capecitabine) was not superior to pFLOT in terms of DFS (1.10, 0.71-1.69) or OS (1.09, 0.69-1.72). Conclusions: pFLOT demonstrated superior efficacy in resectable gastric/GEJ AC, surpassing surgery alone, nCROSS, and other perioperative regimens. The additive role of immunotherapy to pFLOT requires further investigation to refine patient selection and optimize outcomes. Regimen Overall Population GEJ cohort OS DFS OS DFS nPLF+nCRT(EP) 1 (90) 2 (84) 1 (85) NA pFLOT 2 (87) 1 (91) 2 (79) 2 (88) pPembrolizumab+CF/CX 3 (75) 3 (81) 5 (41) - nECX 4 (61) 5 (55) - - pCF 5 (59) 8 (51) 3 (72) - pECF/ECX 6 (47) 6 (55) 7 (40) 3 (57) nECX+aCRT(CX) 7 (45) 7 (52) 9 (31) - nCF 8 (42) 10 (28) 6 (40) - nCROSS 9 (41) 9 (35) 8 (34) 4 (43) pECF/ECX/FLOT+nCRT(F/X) 10 (38) 4 (57) 4 (72) 1 (90) nCRT(CF) 11 (9) 11 (6) - 5 (14) Surgery 12 (7) 12 (5) 10 (5) 6 (9) Data reported as rank (P-score). Abbreviations: n: neoadjuvant; p: perioperative; ECX: epirubicin + cisplatin + capecitabine; CF: cisplatin + fluorouracil; ECF: epirubicin + cisplatin + fluorouracil; aCRT(CX): adjuvant radiotherapy + cisplatin + capecitabine; CRT(F/X): fluorouracil/capecitabine + radiotherapy; CRT(CF): cisplatin + fluorouracil + radiotherapy.

3005 Background: [ 212 Pb]VMT-α-NET, a next generation 212 Pb-based, SSTR2-targeted alpha-particle radiopharmaceutical therapy (RPT), was designed to achieve superior biodistribution via optimized tumor uptake and retention and rapid renal clearance. Results reported here are from the Phase 1/2a first-in-human study [NCT05636618]. Methods: Safety, pharmacokinetics, dosimetry and efficacy using RECIST v1.1 were investigated in the treatment of participants with [ 212 Pb]VMT-α-NET who had SSTR2-expressing, well-differentiated adult NETs of any grade. Participants received ≥1 prior therapy. No prior peptide receptor radionuclide therapy was allowed. The trial has multiple dose cohorts including 92.5 MBq (2.5 mCi, cohort 1) and 185 MBq (5 mCi, cohort 2) of administered activity based on a Bayesian modified toxicity probability interval (mTPI-2) design. Up to 8 participants per cohort were treated with 4 doses of [ 212 Pb]VMT-α-NET for DLT observation. Cohort 2 enrollment was expanded to further define the safety and efficacy profile at this dose level. Results: Nine (9) gastroenteropancreatic NET participants were enrolled into cohorts 1 and 2 for DLT observation. The ninth of these participants was enrolled more than 1 year prior to presentation of these data. Among these participants at the time of abstract submission, no DLTs were observed, and there were no grade 4, 5 or serious adverse events (SAEs). Specifically, no renal insufficiency or dysphagia were observed. Hematologic AEs were low grade and few in number. No treatment discontinuations due to AE occurred. Three (3) of the 7 cohort 2 participants enrolled for DLT observation achieved investigator-assessed partial responses (PRs). Two PRs were unconfirmed at the time of abstract submission. Durable progression-free survival (PFS) was consistently observed. More than 15 additional participants were enrolled in the cohort 2 expansion. Preliminary data for these patients will be reported at the congress. Conclusions: [ 212 Pb]VMT-α-NET is a well-tolerated, next generation RPT showing signs of clinical activity at early dose-levels in this phase 1/2a study. Based on these clinical data, further dose-escalation and development of this promising therapy are warranted. Clinical trial information: NCT05636618 .

4166 Background: GN is a front-line therapy for aPDAC. A Phase I/II study demonstrated that GCN has a higher overall response rate and median overall survival (mOS). Our previous study found no difference in outcomes among patients with DNA damage repair gene mutations; however, stromal gene expression correlated with mOS in patients receiving GCN. Here, we further evaluate differences in the outcomes with GCN and GN by site of biopsy. Methods: PDAC samples (n = 4,463) were analyzed by NGS (NextSeq/NovaSeq) or RNA (NovaSeq) (Caris Life Sciences, Phx, AZ). Expression of stromal and related genes ( ACTA2, ADIRF, HAS2, IL-6, MMP-2, MMP-9, SPARC, STAT3, TBGB1, TGFB2, TGFBR3, IDO1, HLA-DRB4, VEGFB) from different biopsy sites [high expression (H) >50% of RNA transcripts per million] was correlated with outcomes to GCN or GN. mOS was obtained from insurance claims and calculated from first treatment to last contact. The hazard ratio (HR) was calculated by the Cox proportional hazards model, and p-values were calculated using the log-rank test. Results: 4325 patients [primary biopsy (PT), n = 1,878; non-liver metastatic biopsy (N-LM), n = 818; Liver biopsy (LM), n = 1,629] received GN while 138 patients (PT, n = 45; N-LM, n = 28; LM, n = 65) received GCN. GCN was associated with longer mOS than GN [∆: 5.2 months (m), HR: 0.76, 95% CI 0.63-0.92, p = 0.01]. GCN was associated with longer mOS compared to GN in LM (∆: 5.6 m, HR: 0.66, 95% CI 0.50-0.87, p = 0.003), but it was not significant in PT (∆: 4.6 m, p = 0.13) and N-LM (∆: 4.4 m, p = 0.35). Median MMP2 (38.5 vs. 163.1 vs. 162.2), VEGFB (14.4 vs. 16.9 vs. 16.2) and TGFBR3 (11.4 vs. 15 vs. 16.4) expression were lower in LM compared to PT and N-LM while TGFB1 (41.6 vs. 34.5 vs. 39.8) and IL6 (1.61 vs. 1.19 vs. 1.41) expression were highest in LM (p < 0.05). In LM, IL6 -H (∆: -11 m, p = 0.037) and TGFB1 -H (∆: -5.9 m, p = 0.10) were associated with worse post-GCN survival compared to GN (p = 0.82 and p = 0.57). Whereas, in N-LM, TGFBR3 -H trended towards longer post-GCN survival (∆: 12 m, p = 0.18), while ADIRF -H trended towards shorter post-GCN survival (∆: -12 m, p = 0.056) compared to GN (p = 0.42 and p = 0.10). While in PT, MMP2 -H (∆: 11.3m, HR: 0.46, p = 0.16), TGFB1 -H (∆: 11.3 m, HR: 0.33, p = 0.09), HLA-DRB4 -H (∆: 12.9 m, HR: 0.44, p = 0.11) and VEGFB -H (∆: 10.7, HR: 0.34, p = 0.09) trended towards longer post-GCN survival compared to GN ( MMP2 -H, ∆: 3.4 m, p = 0.03, TGFB1 -H, p = 0.661, HLA-DRB4 -H, p = 0.67, VEGFB-H , ∆: 1.3 m, p = 0.03). Conclusions: GCN is associated with improved mOS compared to GN, especially in LM.Stromal gene expression in the liver differs from that in N-LM and the pancreas. While high stromal gene expression trends towards worse post-GCN survival in LM, it is associated with improved survival in N-LM and PT. Further validation is needed to understand the impact of stromal gene expression in different tumor sites on survival outcomes and signature development.