433 Background: Peritoneal metastasis (PM) from gastric cancer (GC) carries a dismal prognosis and remains refractory to systemic therapies. Oncolytic virotherapy offers a novel peritoneal-targeted approach. We evaluated the efficacy of CF33-hNIS, a chimeric orthopoxvirus, alone and in combination with anti–PD-L1 immune checkpoint blockade in an immunocompetent mouse model of gastric cancer peritoneal metastasis (GCPM). Methods: A syngeneic GCPM model was established using ACKPY3944 murine GC cells. Mice received intraperitoneal (IP) CF33-hNIS alone or in combination with intravenous (IV) or IP anti–PD-L1. Tumor regression, survival, and immune responses were assessed. Flow cytometry and immunohistochemistry characterized CD3⁺ T-cell subsets in the peritoneal cavity and tumor microenvironment. Complete tumor regression (CTR) mice were rechallenged with ACKPY3944 cells to evaluate memory T-cell responses. Results: IP CF33-hNIS monotherapy significantly prolonged survival and increased CD3⁺ and CD8⁺ T-cell infiltration in both peritoneal fluid and tumor tissue. The most effective regimen—a single high-dose CF33-hNIS (10⁸ pfu) combined with IP anti–PD-L1 (Combo 2)—achieved 75% CTR. Mice with CTR rejected tumor rechallenge and exhibited marked expansion of effector and central memory T cells in the peritoneal cavity and spleen. Conclusions: IP CF33-hNIS exerts potent anti-tumor activity in GCPM, enhanced by concurrent IP anti–PD-L1. The high-dose Combo 2 strategy induces durable tumor-specific immunity and provides strong rationale for clinical translation of simplified, peritoneal-targeted oncolytic viro-immunotherapy in gastric cancer.

BACKGROUND:Implementation of remote robotic-assisted surgery (rRAS) has the potential to significantly improve access to high-quality surgical care for patients worldwide. Advances in robotic systems and telecommunications now enable highly reliable, low latency, and cybersecure connectivity. These technological developments, together with the broader adoption of telemedicine, have driven an increasing interest in the implementation of rRAS. METHODS:The Clinical Robotic Surgery Association (CRSA) convened a conference to develop international clinical recommendations for rRAS using the Danish Model of Consensus. The society identified five key issue categories and invited a panel of experts to address specific questions for each. Panel members and a jury of 10 unbiased, non-expert in rRAS professionals participated in a day-long conference on November 19, 2025 (Los Angeles, USA). During the conference, participants presented, discussed, and reached consensus on specific guidelines relevant to each category. Immediately after the conference, the jury reviewed and approved the recommended guidelines. RESULTS:Multiple recommendations were approved for each of the following categories: Operating Models, Roles and Responsibilities (2 recommendations), Clinical Pathway (2 recommendations), Emergency Management (8 recommendations), Technical Considerations (5 recommendations), and Medico-legal and Ethical Considerations (4 recommendations). CONCLUSIONS:There was consensus that with recent advances in telecommunication and robotic technologies, rRAS can be offered safely and effectively if the identified safeguards are realized. Adoption of rRAS is expected to continue advancing rapidly.

Tobacco cessation is an important supportive component of cancer care. We developed a novel program to overcome cancer patient barriers to tobacco cessation and improve outcomes. The personal pathways to success (PPS) program consisted of core components of a motivational interview, an instructional video on tobacco cessation, referral to cessation consultation, and/or an offer of cessation medications. Patients who agreed to participate in PPS were also offered the choice of 30 additional PPS supplemental support cessation services. Participants were active smokers before planned surgery at City of Hope (COH) and were referred to the PPS program. We compared tobacco use in patients who participated in PPS with supplemental support services to patients who did not participate. We compared non-Hispanic white patients to patients from minority groups. Evaluations of tobacco use were performed before surgery in all patients, and at 30 days, 3, 6, 9, and 12 months after surgery in PPS participants, and at 12 months in non-participants. Among 70 patients, 7 were re-directed by insurance to a non-COH provider. Among the other 63 patients, 58 completed the motivational interview (acceptability rate 92

BACKGROUND:Since its inception, surgical oncology training has emphasized the treatment of complex tumors without restriction to a specific anatomic region. As the complexity of cancer care increases, it is unclear whether this broad-based training model remains optimal. We set out to characterize how fellowship prepares graduates for clinical practice and to identify trends in surgical oncology training and practice. METHODS:A 24-item survey was sent to graduates of an academic surgical oncology training program between the years 1981 and 2022. Questions focused on preparedness for practice upon graduation, current clinical and non-clinical activities, and the evolution of respondents' practice since completion of fellowship. RESULTS:Respondents indicated that they felt generally well prepared to treat a wide range of malignancies. Post-2013 graduates, felt significantly better prepared to treat peritoneal surface and gynecologic malignancies and to perform robotic surgery. In contrast, pre-2013 graduates indicated greater preparedness for the treatment of melanoma, extremity sarcoma, head and neck, esophageal and thoracic malignancies (p 0.05). Respondents practiced broadly, treating a median of 5 disease sites, although 36% dedicated more than half of their time to a single site. Despite the lack of formalized leadership training, 40.9% of graduates were involved in leadership positions. CONCLUSIONS:Our findings confirm that the existing surgical oncology training positions trainees well for practice, even in a landscape with many partially overlapping and competing surgical fellowships. In addition, many graduates are engaged in administrative and leadership roles suggesting that surgical oncologists may benefit from formalized leadership training during fellowship.

Glioblastoma is the most aggressive primary brain tumor with no cure, largely because of tumor heterogeneity and immunosuppressive tumor microenvironment. Chimeric antigen receptor (CAR)-T cell therapy is highly effective in blood cancers but exhibits limited efficacy in glioblastoma due to heterogeneous tumor antigen expression, antigen loss and poor persistence of tumor-targeting immune cells in glioblastoma. Here we show a multimodal immunotherapy strategy that integrates engineered immune cells with oncolytic viruses to overcome these barriers. We have developed bispecific CAR-T and CAR-NK cells in combination with oncolytic virus that delivers two tumor antigens to glioblastoma cells for effective CAR targeting. Moreover, oncolytic virus armed with membrane-bound interleukin-15 and interleukin-21 enhances immune cell expansion/persistence and cytotoxic activity. This combined approach improves anti-tumor efficacy in vitro and in vivo by limiting immune escape and enhancing anti-tumor immunity. Together, these findings establish a promising platform for multimodal immunotherapy targeting glioblastoma and other solid tumors.

Peritoneal metastasis (PM) is the leading cause of treatment failure and death from gastric cancer (GC). We evaluated the antitumor and immunogenic effects of CF17, an oncolytic chimeric orthopoxvirus, in a novel syngeneic mouse model of GCPM. CF17 was tested in mouse GC cell lines (ACKPY3944 and ACKPY4113) for viral replication and cytotoxicity. A syngeneic mouse model of PM was established in C57BL/6 mice via intraperitoneal (IP) implantation of 1 × 106 ACKPY3944-ffluc cells. Mice were treated with either IP CF17 or PBS. Peritoneal tumor burden was monitored by bioluminescence imaging. Immune profiles of peritoneal washings and tumors were assessed by flow cytometry and immunohistochemistry. CF17 infected, replicated in, and killed ACKPY3944 and ACKPY4113 cells in vitro. Mice treated with IP CF17 showed a significant decrease in tumor burden (p < 0.05) and prolonged survival (p < 0.001). CF17 treatment significantly enhanced leukocyte infiltration, including CD4+ and CD8+ cells, into the tumor microenvironment of the peritoneal cavities and solid tumors. Overall, these results demonstrate that CF17 has potent anti-tumor activity and immunogenicity in a syngeneic mouse model of GCPM. These data provide a framework to support future studies to optimize CF17-based immunotherapeutic approaches for GCPM.

Cholangiocarcinoma (CCA) is a highly lethal, heterogeneous malignancy arising from the biliary tract. Although the prevalence of CCA is relatively low, its incidence has increased in the last few decades, and the overall prognosis is poor. Surgical resection remains the most efficacious treatment modality for CCA. However, due to its aggressive nature and often asymptomatic presentation, most patients are first diagnosed with advanced disease, precluding them from curative intervention. Moreover, due to its heterogeneity at the molecular, genomic, and epigenetic levels, drug treatment of CCA remains challenging. In this review, we discuss the current standard drug treatment approaches, recent breakthroughs, and promising new therapeutics for CCA. We summarize key clinical data for the standard first-line chemotherapy regimen and its efficacy and resistance mechanisms, along with more recent studies supporting or proposing second-line treatments. We highlight landmark clinical trials, including ABC-02, which established gemcitabine-cisplatin (GC) as the first-line regimen against biliary cancers. Additionally, we discuss recent findings on the susceptibility of CCA against targeted therapies and other immunologic molecules, including results from the KEYNOTE-966 and TOPAZ-1 clinical trials. Finally, we critically analyze new therapeutics in the preclinical and clinical space, such as CAR-T cells and oncolytic viruses that may be effective against CCA.

PURPOSE:We evaluated the role of complete cytoreductive surgery (CRS) for locoregional disease control in patients with colorectal cancer with peritoneal metastases (CRC-PM) and concurrent extraperitoneal metastases (EPM). METHODS:Institutional data identified patients with CC-0/1 CRS for CRC-PM. Patients with peritoneal disease only (PDO) were compared with those with concomitant EPM. Co-primary outcomes were progression-free survival (PFS) and peritoneal progression-free survival (p-PFS). The secondary outcome was overall survival (OS). Covariate imbalance was addressed using entropy balancing. Survival was analyzed using a weighted Cox proportional hazards model. Subgroup analyses were performed to identify favorable prognostic groups. RESULTS:In total, 83 patients were included: 31 (37.4%) had EPM. Baseline characteristics were comparable. Within the EPM cohort, liver-only metastases were most common (58%), followed by lung-only metastases (26%). EPM were managed at index CRS in 61%, before CRS in 19%, and deferred or untreated in 19% of patients. Unadjusted analyses demonstrated comparable median OS (PDO vs. EPM: 39 vs. 34 months, p = 0.551) and median p-PFS (PDO vs. EPM: 17 vs. 15 months, p = 0.346) but longer median PFS in the PDO group (14 vs. 5 months, p<0.001). After entropy balancing, patients with EPM had worse OS (31.6 vs. 38.7 months; hazard ratio [HR] 2.12; 95% confidence interval [CI] 1.02-4.37; p < 0.05) and PFS (5.0 vs.12.8 months; HR 2.7; 95% CI 1.58-4.5; p < 0.001) but similar p-PFS (13.4 vs.14.9 months; HR 1.10; 95% CI 0.58-1.77; p = 0.622). Subgroup analyses demonstrated comparable OS and p-PFS for patients with PDO and those with single-site liver or lung EPM. CONCLUSION:Complete CRS provides durable locoregional disease control in patients with EPM.

Background Peritoneal metastasis (PM) from gastric cancer (GC) is associated with poor prognosis and limited treatment options. We investigated a novel peritoneal-targeted therapy using CF33-human sodium iodide symporter (hNIS), a chimeric orthopoxvirus, combined with anti-PD-L1 immune checkpoint blockade in an immunocompetent mouse model of GCPM.Methods We evaluated replication and cytotoxicity of CF33-hNIS in human and murine GC cell lines. We assessed a syngeneic mouse model of PM using the transgenic mouse GC ACKPY3944 cells to test the efficacy of intraperitoneal (IP) CF33-hNIS alone and combined with intravenous or IP anti-PD-L1. Next, we performed flow cytometry and immunohistochemistry to analyze immune cell populations of CD3+ T cell subsets in the peritoneal cavity and tumor microenvironment. Mice that showed complete tumor regression (CTR) were rechallenged with ACKPY3944 cells to assess memory T cell responses.Results CF33-hNIS efficiently infected and killed GC cells. In vivo, IP CF33-hNIS alone significantly prolonged survival and increased infiltration of CD3+ and CD8+ T cells within the peritoneal cavity and solid tumor. The most pronounced therapeutic effect was observed with a single high-dose of CF33-hNIS (108 plaque-forming units) combined with IP anti-PD-L1 (Combo 2) with 75% CTR. Notably, mice with CTR rejected tumor rechallenge, exhibiting significantly elevated effector and central memory T cell populations in the peritoneal cavity and spleen. IP CF33-hNIS demonstrates robust anti-tumor efficacy against GCPM, particularly when combined with IP anti-PD-L1 in the high-dose Combo 2 regimen.Conclusions These findings support a simplified, high-dose IP treatment strategy to overcome immune resistance in GCPM and provide a strong rationale for future clinical evaluation.

This multisociety, multidisciplinary consensus—formally endorsed by the European Society of Surgical Oncology, the Cardiovascular and Interventional Radiological Society of Europe, and the Society of Interventional Oncology—was developed to standardise the assessment of ablation margins in liver tumour thermal ablation. A modified Delphi process, consisting of two online surveys and a hybrid (online and in-person meeting in Innsbruk) consensus meeting of 72 experts from North America, South America, Europe, and Asia. Formal consensus was reached for 150 (75%) of 199 statements. Strong agreement was observed between interventional and surgical oncologists, with only 12 (6%) of 199 statements showing significantly different ratings. Participants agreed that ablation margins should be assessed and documented for every treated tumour. Margins should be assessed quantitatively in three dimensions, with contrast-enhanced CT or MRI, preferably intraprocedurally with ablation confirmation software. Ablation margins should be categorised as A0 (tumour completely covered with sufficient margin), A1 (tumour completely covered but insufficient margin), or A2 (portion of tumour remains unablated). This effort is, to our knowledge, the first international consensus initiative to define best-practice recommendations for margin assessment in liver tumour thermal ablation to standardise practices, aiming to improve and promote uniform outcomes.

BACKGROUND AND OBJECTIVES:Simultaneous rectal and hepatic resection for metastatic rectal cancer is less commonly performed due to concerns about safety, and the oncological outcomes are less well described. The objective of this study is to examine peri-operative and oncological outcomes for patients with rectal cancer liver metastases (RCLM) after simultaneous resection. METHODS:A single-center, retrospective analysis of patients who underwent curative-intent, simultaneous total mesorectal excision (TME) and hepatectomy for RCLM (January 2011 to May 2024). Post-operative safety and oncological outcomes were examined. RESULTS:92 patients were analyzed, with the majority having high burden of hepatic metastases. No deaths occurred. 14 patients (15%) had > Clavien-Dindo Grade 3 complication, drainage of perihepatic fluid in eight patients (9%), and an anastomotic dehiscence in three patients (3%). Median follow up was 51 mo, and median OS was 70 mo, RFS was 10 mo, and H-RFS was 17 mo. Positive hepatic margin was associated with decreased OS, while a high Clinical Risk Score, a high Tumor Burden Score, and > 6 cycles of neoadjuvant chemotherapy were associated with decreased RFS and H-RFS. CONCLUSION:Simultaneous resection of RCLM was associated with peri-operative safety and long term survival in patients with high-risk disease, and can be reasonably offered in appropriate setting.

Importance:Difficult cholecystectomies are associated with a higher risk of severe bilio-vascular injuries. Observations:Obesity, cirrhosis, high American Society of Anesthesiologists score, previous abdominal operations, and presence of acute cholecystitis or common bile duct stones are associated with difficult cholecystectomies. On imaging, thickened gallbladder wall, pericholecystic fluid, and an impacted gallstone are associated with difficult cholecystectomies. In challenging operations, the use of imaging (intraoperative cholangiography, intraoperative ultrasound, near-infrared cholangiography) is recommended. If the critical view of the hepatocystic triangle cannot be safely achieved, bailout strategies, such as tube cholecystostomy, subtotal cholecystectomy, or an anterograde approach, should be considered. Conversion to open surgery should be considered for significant bleeding, cholecystoenteric fistula, Mirizzi syndrome, or malignancy. Seeking advice or assistance from another surgeon is recommended when conditions are challenging. Conclusions and Relevance:Knowledge of perioperative and intraoperative adjuncts and alternative surgical options aid surgeons in performing difficult cholecystectomies safely.

432 Background: Gastric cancer peritoneal metastasis (GCPM) has limited therapeutic options and dismal prognosis. Oncolytic virotherapy (OVT) efficacy is critically shaped by its interaction with TAMs. CF33, a novel chimeric orthopoxvirus, demonstrates cytotoxicity against gastric cancer (GC) cells, but its effects on M2-polarized tumor-associated macrophages (TAMs)—the dominant immune-suppressive component of the peritoneal tumor microenvironment (TME)—remain poorly defined. Methods: Patient-derived ascitic cells from GCPM were treated with CF33-GFP and analyzed by flow cytometry. Human PBMC-derived M2 macrophages were exposed to CF33-OVs to assess viral infection/replication, cytotoxicity, death pathways, and M2→M1 phenotypic switching, using annexin V/PI staining, microscopy, MTS assays, TEM, western blotting, RNA-seq, cytokine multiplexing, and migration assays. In vivo effects were validated in a syngeneic mouse model of GCPM (ACKPY3944), with TAM modulation assessed by flow cytometry and immunohistochemistry. Results: CF33-OVs selectively infected and replicated in M2 macrophages, inducing CELL death through intrinsic apoptotic and autophagic pathways, with activation of p-TBK1, p-Akt, p38 MAPK, and CDK4/6 signaling. RNA-seq revealed reprogramming of M2 macrophages toward an M1 phenotype, accompanied by upregulation of pro-inflammatory cytokines/chemokines and enhanced immune cell migration. Ex vivo, CF33-OVs eliminated TAMs in patient-derived ascites, and in vivo, CF33-hNIS effectively depleted TAMs in peritoneal cavity of syngeneic GCPM tumors. Conclusions: CF33-hNIS directly targets and eliminates TAMs while reprogramming the peritoneal TME from immunosuppressive (“cold”) to immune-active (“hot”). By simultaneously killing GC cells and remodeling TAM biology, CF33-hNIS enhances anti-tumor immunity and represents a promising therapeutic strategy for GCPM.

413 Background: The role of neoadjuvant chemotherapy (NAC) in resectable, locally advanced gastric cancer is debated, with wide variation in adoption between Asian and Western countries. The impact of these diverse practices on perioperative and long-term outcomes is not well defined. Methods: We analyzed 23,805 patients who underwent resection from 10 high-volume gastric cancer centers across Asia, Europe and North America from January 3, 2005 to March 11, 2024. Patients with ≥T2 tumors undergoing radical gastrectomy with or without NAC were compared. Propensity score matching (3:1) adjusted for age, comorbidity, clinical stage, and histology. Results: After matching 1,017 patients (353 NAC, 664 non-NAC) were evaluated. In the West FLOT was the most common regimen (56.3%), while the East had more variability but overall used a combination of taxane and platinum agent (63.5%), with SOX being most common (17.9%). NAC patients more often underwent total gastrectomy (31.2% vs 23.5%, p<0.001), a more extensive lymph node dissection with D2 (62.7% vs 51.9%, p<0.001), and conversion to open surgery (2.93% vs 0.7%, p=0.008). NAC down staged tumors, with fewer pT4a tumors (14.0% vs 20.7%, p<0.001), and more T0 tumors (4.58% vs 0%, p<0.001). Despite these effects, pathologic nodal stage and margin status were similar; and the perioperative-hospital mortality (0.34% vs 0%, p=0.182) and complication rates did not differ. Moreover, overall recurrence rates (19.9% vs 16.4%, p=0.176) also did not differ. Interestingly, NAC patients more often recurred in the peritoneum (57.1% vs 36.4%, p=0.03) and less often in distant sites (8.2% vs 25.85%, p=0.03). Median follow up was 36.4 months (range 0.16 to 144.4 months). Median disease-free survival (10.1 vs 10.6 months, p=0.29) and overall survival (14.5 vs 17.8 months, p=0.61) were similar. Conclusions: In one of the largest and most ethnically diverse international propensity-matched analyses to date, NAC achieved tumor downstaging but did not improve disease-free or overall survival compared to upfront surgery. Distinct recurrence patterns after NAC highlight biological heterogeneity, underscoring the need for tailored strategies to optimize timing systemic therapy in locally advanced gastric cancer. Global real-life oncologic outcomes of NAC versus non-NAC in locally advanced gastric cancer patients at high-volume centers. Non-NACn = 664 NACn = 353 p-value Recurrence, n (%) 106 (16.4) 68 (19.9) 0.176 Recurrence location, n (%) 0.030 Peritoneum 24 (36.4) 28 (57.1) Distant 17 (25.8) 4 (8.2) Local 3 (4.6) 2 (4.1) Distant lymph node 14 (21.2) 7 (14.3) Multiple 5 (7.6) 8 (16.3) Overall survival median, months (IQR) 17.8 (11.5 - 24.4) 14.5 (8.2 - 21.4) 0.613 Disease free survival median, months (IQR) 10.6 (5.7 - 18.8) 10.1 (5.9 - 16.5) 0.286 IQR: Interquartile range, NAC: Neoadjuvant chemotherapy.

Thermal ablation offers a safer, less invasive, and more cost-effective curative-intent treatment for selected patients with primary and metastatic liver tumours than surgery; when done with appropriate technique, ablation can deliver similar oncological outcomes. However, effectiveness in routine practice varies because structured training, planning, and procedural governance remain scarce. These international multidisciplinary, multi-society guidelines—formally endorsed by the European Society of Surgical Oncology, the Cardiovascular and Interventional Radiological Society of Europe, and the Society of Interventional Oncology—define key domains contributing to procedural difficulty and practice variation in liver tumour thermal ablation. A Delphi consensus initiative held in Innsbruck, Austria, engaged 72 experts across three iterative rounds of scoring across 135 statements grouped into five domains: credentialing, indications, approach, procedural factors, and safety measures. Consensus was achieved for 94 (70%) of 135 statements. The least invasive route—typically percutaneous—should be prioritised, and margin adequacy was reaffirmed as the principal technical goal. Procedural difficulty was considered context-dependent, shaped by tumour factors, institutional infrastructure, and operator experience. Organ displacement techniques were endorsed to maintain safety and expand treatable indications. Complex ablations should be done by experienced operators (more than 100 previous cases), with programmes underpinned by structured training, multidisciplinary team participation, and routine audit. Future efforts should develop and validate practical tools such as difficulty scoring systems, standardised procedural reporting templates, and comprehensive training curricula to improve consistency, standardisation, and clinical outcomes globally.