Introduction Shared decision-making (SDM) is a tenet in patient centered care, but assessment of SDM for pancreatic cancer surgery has been limited. The aim of this study is to identify studies which utilized quantitative assessments of SDM for pancreatic cancer surgery. Methods We searched four databases from inception until March 2025. Abstracts and titles were screened, and full texts were analyzed by two readers (B.O.W., M.A.V.). Data on author, year, cancer population, location, and assessment method were collected. Only studies that included at least one quantitative assessment were included. Items from each assessment were extracted and coded with top-level and subcodes to identify themes. Results Title and abstract screening of 134 studies yielded 6 studies which met inclusion criteria. Review of these studies revealed 7 validated quantitative assessments of SDM, of which 3 were patient reported and 4 require external observation. shared decision making questionnaire-9 was most frequently used (5/6) and the only instrument used by more than one study. We identified four themes and ten subthemes across all 7 instruments. Of the subthemes, “Eliciting treatment preferences” was measured by every quantitative assessment, “advantages and disadvantages of options” was measured by 6 of 7 assessments, and “presenting options” was measured by 5 of 7 assessments. Conclusions The assessments used for measuring SDM in pancreatic cancer surgery in prior research studies are not specifically designed for cancer surgery SDM. Findings from this scoping review highlight discrepancy between current assessments of SDM and needs of SDM for pancreatic cancer surgery.

Postoperative pancreatic fistula (POPF) is a major contributor to morbidity and mortality after pancreaticoduodenectomy (PD)1. Externalized pancreatic stents decrease the incidence and severity of POPF after PD2–6, but their feasibility has not been demonstrated in robotic PD. We present our method of externalized pancreatic stent placement during robotic PD and report our initial experience. This video demonstrates our technique of using an externalized pancreatic stent during robotic PD. We conducted a retrospective review of patients who underwent robotic PD with externalized pancreatic duct stent placement at a single academic institution. Fistula risk was graded using the Fistula Risk Score (FRS)7 and the Alternative FRS8, and postoperative outcomes were recorded. Of 67 consecutive patients, 44.8

INTRODUCTION:ON-Q pumps, or surgically placed wound catheters, provide analgesia without the side effects of epidural catheters. This study aimed to evaluate perioperative outcomes, including total postoperative oral morphine milligram equivalents (MMEs), perioperative intravenous (IV) fluid volume, and maximum patient-reported pain scale values, in pancreatic or hepatic resection patients on an Enhanced Recovery After Surgery (ERAS) pathway with ON-Q pumps versus other perioperative pain modalities. METHODS:Patients undergoing ERAS protocol pancreatic or hepatic resection at our institution from January 2019 to March 2022 were included. Patients were categorized based on ON-Q pump, epidural, or transversus abdominis plane (TAP) block/local anesthetic. Total postoperative oral morphine milligram equivalents (MMEs), perioperative intravenous (IV) fluid volume, and maximum patient-reported pain scale values were analyzed. RESULTS:Of 537 included patients, 249 (46%) received an epidural, 116 (22%) received an ON-Q pump, and 172 (32%) received a TAP block/local anesthetic. ON-Q pump patients required significantly less IV fluids (2,933 mL) compared to 3,379 mL for epidural and 3,278 mL for TAP block/local anesthetic patients (p=0.0037). There was no significant difference in MME requirement or pain scores across pain modalities. CONCLUSIONS:ON-Q pump patients had significantly lower IV fluid requirements, though similar pain scores and MME requirements as epidurals or TAP blocks/local anesthetics. The use of ON-Q pumps as a main perioperative pain modality should be considered for ERAS pathway patients.

12099 Background: Cancer interventions are often discussed amongst providers and presented to patients within the dichotomy of “curative” vs. “palliative” interventions. However, as understanding of cancer biology has shifted and as cancer treatments have evolved, some cancers have become chronic diseases for which surgery may have a non-curative but disease-targeted role. Despite new paradigms of cancer care, language has not evolved to reflect new goals of cancer surgery. Methods: Semi-structured interviews were conducted with cancer surgeons from throughout the U.S. via purposive and snowball sampling. Interviews included discussions of two hypothetical scenarios describing non-curative surgical operations and discussion of the term “disease-controlling” surgery as a category of neither palliative nor curative surgical intent. Transcribed and de-identified interviews were analyzed inductively using grounded theory. Results: 18 surgeons from 16 institutions were interviewed. Surgeons collectively outlined how changes in the paradigm of cancer treatment have resulted in challenges describing intent of cancer surgery. Specifically, responses to the term “disease controlling” surgery elicited examples of cancer pathologies and treatment courses which fail to fit existing treatment-intent language and which captured new roles for surgery in cancer treatment paradigms. These roles of surgery include "surgery as curative treatment" (including both curative intent with probability of cure and curative intent with possibility of cure), "surgery as adjuvant treatment" (targeted surgery to assist systemic therapies with possible change in disease course), and "surgery as palliative treatment" (symptom relief surgery without possible change in disease course). Within the 'targeted surgery' category, participants described expanded surgical roles for numerous metastatic diseases including debulking for improved systemic therapy efficacy, resection of treatment-resistant disease sites, and "resetting the clock" for indolent tumors. These operations require multidisciplinary coordination and understanding of available systemic treatments, as surgical goals are increasingly defined by each patient's broader treatment trajectory. Conclusions: Traditional “curative” vs. “palliative” surgical intent categories inadequately describe contemporary cancer surgery. The emergence of life-extending but non-curative treatments necessitates new language frameworks that better align with current understandings of cancer biology and new treatment modalities. New language is necessary to facilitate clearer communication between providers and patients about surgical goals and expected outcomes and to allow for better research evaluating whether surgical treatments achieve those goals and outcomes.

Background and Methods Cancer interventions are traditionally described as either "curative" or "palliative," but evolving cancer biology and new treatments have transformed some cancers into chronic diseases where surgery plays a non-curative, disease-targeted role. We conducted semi-structured interviews with cancer surgeons via purposive snowball sampling, exploring two hypothetical scenarios and discussing "disease-control" surgery as a category of neither palliative nor curative surgical intent. Interviews were thematically analyzed.Results Eighteen surgeons from 16 US institutions described how evolving cancer treatment paradigms challenge existing language for surgical intent. "Disease-control" surgery captured new adjuvant surgical roles including debulking to improve systemic therapy efficacy, resection of treatment-resistant disease, and "resetting the clock" for indolent tumors. Surgical goals are increasingly defined by individual patients' broader multidisciplinary treatment trajectory.Conclusions Traditional "curative" versus "palliative" categories inadequately describe contemporary cancer surgery. New frameworks aligned with current understandings of cancer biology and new treatment modalities may facilitate clearer communication about surgical goals and enable developing appropriate research outcome measures.Discussion These findings highlight a need for standardized surgical intent terminology. Broader validation through multidisciplinary stakeholder engagement is needed to refine and implement this proposed framework.

Pancreatic ductal adenocarcinoma (PDAC) is resistant to current immunotherapies and lacks effective anti-tumor CD8+ T cells, which is potentially due to insufficient cross-presentation by cDC1s. Here, we combine a STING agonist with anti-CTLA-4 and anti-PD-1 to achieve durable remissions and immunologic memory in multiple mouse models of poorly immunogenic PDAC. We find that tumor control does not depend on CD8+ T cells or tumor cell MHC expression but instead requires IFNγ-producing CD4+ T cells (Th1s) that are primed by dendritic cells in lymph nodes. The triple combination immunotherapy induces an accumulation of activated cDC2s carrying tumor antigen into tumor-draining lymph nodes; cDC2s are required for orthotopic tumor clearance. Intratumoral CD4+ T cells and cDC2s remain present in treatment-naive and chemotherapy-exposed human PDAC. In chemotherapy-exposed patients’ blood, cDC2s outnumber cDC1s by 10-fold. Therefore, therapeutic targeting of the cDC2-CD4+ T cell-IFNγ axis could be efficacious in PDAC.

BACKGROUND:Colorectal cancer most commonly metastasizes to the liver. While various treatment strategies have been developed, surgical management of these patients has vital implications on the prognosis and survival of this group of patients. There remains a need for a consensus guideline regarding the surgical evaluation and management of patients with colorectal liver metastases (CRLM). METHODS:This review article is a consensus guideline established by the members of the AHPBA Professional Standards Committee, as an amalgamation of existent literature and a guide to surgeons managing this complex disease. RESULTS:These guidelines reports the benefits and shortcomings of various diagnostic modalities including imaging and next-generation sequencing in the management of patients with CRLM. While surgery has established survival benefits in patients with resectable disease, this report notes the importance of treatment sequencing with non-surgical modalities as well as between colon and liver resection. Finally, the guidelines address the various treatment modalities for patients with unresectable disease, that may have significant impact on survival. CONCLUSION:CRLM is a complex diagnosis which warrants multidisciplinary approach with early surgical involvement in both assessment and management of the disease, to optimize patient outcomes and survival.

Biliary tract neoplasms include a diverse set of benign and malignant entities that share both clinical presentations and imaging features. Radiologists need to understand the diagnostic features of these neoplasms to recognize them at initial diagnosis, and we must also provide key information to our surgical and oncology colleagues to facilitate proper management. This work reviews the most important intrahepatic and extrahepatic biliary neoplasms with an emphasis on radiological findings and differentiating features. This work also reviews normal anatomy and key variants of the biliary tree, arterial supply, and venous drainage that impact treatment planning for these entities. Assessment of tumor extent, involvement of critical anatomy, and differential diagnoses are also discussed. This work will support readers in their understanding of biliary tract neoplasms and in the delivery of actionable radiology reports as part of an integrated multidisciplinary care team.

Young-onset pancreatic cancer is increasing in incidence. Age is the strongest risk factor for pancreatic cancer; yet, tobacco smoking and inherited genetic factors are known to influence disease risk, particularly in younger individuals. To investigate how aging, tobacco exposure, and inherited susceptibility contribute to disease onset, we analyzed germline and somatic whole-genome, whole-exome, and targeted exome sequencing data from >1000 patients with pancreatic cancer across multiple cohorts from local and publicly available datasets. Mutational signature analyses quantified endogenous (e.g., aging-related) and exogenous (e.g., tobacco-related) mutational processes, which were assessed by age at diagnosis and smoking status. In a subset of tumors with DNA methylation data, we applied an epigenetic mitotic clock to estimate stem cell division rates based on age-related methylation at CpG-rich promoters. We also identified pathogenic or likely pathogenic (P/LP) germline variants in 21 pancreatic cancer risk genes using ClinVar annotations, evaluated somatic second hits in matched tumors, and calculated a weighted polygenic risk score (PRS) from 22 known low-penetrance susceptibility variants, defining a higher PRS as above the median in healthy individuals. In non-hypermutated tumors, total somatic mutation burden significantly increased with age, primarily driven by clock-like signatures (e.g., SBS1, SBS5, ID1, ID2, ID5). These signatures accounted for an estimated 78% of mutations in older-onset cases (>60 years), increasingly accounting for mutations in main driver genes (KRAS, CDKN2A, SMAD4, TP53). In contrast, smoking-related mutational changes were exclusive to young-onset cases (≤60 years). Young-onset smokers had elevated mutation burdens despite lacking the canonical tobacco signature (SBS4), instead showing increased SBS1 and ID2 signatures, linked to stem cell divisions and DNA replication, as well as higher stem cell division rates inferred from epigenomic analyses. Young smokers also had higher frequencies of TP53 mutations compared to non-smokers (83% vs. 64%; P=.001), particularly missense mutations at CpG sites. Additionally, P/LP germline variants were more frequent in young-onset than older-onset cases (13% vs. 7%; P=.002), with enrichment most evident for BRCA2, and contributed to younger onset only when accompanied by a somatic second hit. A higher PRS was modestly associated with reduced median age of cancer onset (by 4 years), with greater reductions when combined with smoking (7 years earlier) or P/LP variants (14 years earlier), compared to patients with neither of these factors. Our findings support a multifactorial model for pancreatic cancer development: aging-related mutational processes drive older-onset disease, while young-onset disease is more strongly influenced by environmental and inherited factors. These insights have important implications for risk stratification and interception strategies across age groups. Chen Yuan, Harshabad Singh, Kevin S. Kapner, Andressa Dias Costa, Anuradha B. Chittenden, Xinran Qi, Vidya Madineedi, Leigh Culnane, Lauren K. Brais, Douglas A. Rubinson, James M. Cleary, Brandon M. Huffman, Joseph D. Mancias, Thomas E. Clancy, Simona Cristea, Kimmie Ng, Matthew B. Yurgelun, David C. Linehan, Richard F. Dunne, Albert C. Koong, Daniel T. Chang, Aram F. Hezel, Andrew J. Aguirre, Jonathan A. Nowak, Brian M. Wolpin. Young- and older-onset pancreatic cancers arise through distinct mechanisms: Insights from genomic and germline analyses [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr B075.

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Purpose/Objective(s) Surgery remains the only curative option for pancreatic cancer, but few patients have resectable disease at diagnosis. Most present with borderline resectable pancreatic cancer (BRPC) or unresectable tumors. The treatment goal for BRPC is to reduce the local disease burden to enable resection. The choice of the appropriate neoadjuvant therapy to reach this goal is controversial but often includes a combination of chemotherapy, conventional radiation therapy, or stereotactic body radiation therapy (SBRT). This study reports the outcomes of patients with BRPC who are treated with neoadjuvant SBRT. Materials/Methods We conducted a retrospective study of consecutive patients treated with SBRT for a diagnosis of BRPC categorized according to NCCN criteria. Patients were treated at a single institution from April 2015 through July 2020. The primary outcome was completion of surgical resection and the association between this outcome and patient factors or neoadjuvant treatment details was investigated via logistic regression. Surgical outcomes such as R0 resection rate were recorded, as well as oncologic outcomes including survival and disease progression. Results Our analysis included 57 patients with a follow-up of 16.5 months following diagnosis. Most patients (50/57) had tumors located in the head/uncinate process. The mean tumor size was 3.1cm. Vascular involvement was limited to one vessel in 26 patients, two vessels in 27 patients, and three vessels in 4 patients. Before SBRT, all patients received neoadjuvant chemotherapy (median of 8 chemotherapy cycles). Most (48/57) received FOLFIRINOX or gemcitabine/nab-paclitaxel (7/57). The median SBRT dose was 36Gy. The median overall survival from the time of diagnosis was 18.0 months (95% confidence interval (95CI): 15.2-21.2), and the median progression-free survival was 11.9 months (95CI = 11.0-14.0). Of the 57 patients, 29 completed surgical resection (26 R0 resections), while 28 patients did not complete surgery due to advanced or metastatic disease. On both univariable (odds ratio (OR) 5.54, P = 0.006) and multivariable (OR 7.58, P = 0.005) analyses, a cumulative radiation dose of 36Gy or higher was associated with the completion of surgical resection. Other factors including age, gender, performance status, tumor location, neoadjuvant chemotherapy regimen, tumor size, and number of involved vessels did not have an association with the completion of surgical resection. Conclusion In this single-institution study of BRPC patients treated with SBRT, approximately half of the cohort reached the goal of surgical resection, most of which were R0 resections. Of the patient factors and treatment parameters evaluated, elevated cumulative radiation dose was the only factor associated with the completion of surgical resection. These data contribute to the evolving discussion on the most effective approaches to the management of BRPC.

AbstractPurpose: Pancreatic ductal adenocarcinoma (PDAC) trials have evaluated CTLA-4 and/or PD-(L)1 blockade in patients with advanced disease in which bulky tumor burden and limited time to develop antitumor T cells may have contributed to poor clinical efficacy. Here, we evaluated peripheral blood and tumor T cells from patients with PDAC receiving neoadjuvant chemoradiation plus anti–PD-1 (pembrolizumab) versus chemoradiation alone. We analyzed whether PD-1 blockade successfully reactivated T cells in the blood and/or tumor to determine whether lack of clinical benefit could be explained by lack of reactivated T cells versus other factors. Experimental Design: We used single-cell transcriptional profiling and TCR clonotype tracking to identify TCR clonotypes from blood that match clonotypes in the tumor. Results: PD-1 blockade increases the flux of TCR clonotypes entering cell cycle and induces an IFNγ signature like that seen in patients with other GI malignancies who respond to PD-1 blockade. However, these reactivated T cells have a robust signature of NF-κB signaling not seen in cases of PD-1 antibody response. Among paired samples between blood and tumor, several of the newly cycling clonotypes matched activated T-cell clonotypes observed in the tumor. Conclusions: Cytotoxic T cells in the blood of patients with PDAC remain sensitive to reinvigoration by PD-1 blockade, and some have tumor-recognizing potential. Although these T cells proliferate and have a signature of IFN exposure, they also upregulate NF-κB signaling, which potentially counteracts the beneficial effects of anti–PD-1 reinvigoration and marks these T cells as non-productive contributors to antitumor immunity. See related commentary by Lander and DeNardo, p. 474

Mutational frequency KRAS WT vs KRAS MUT

Objective Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed at an advanced stage. Liquid biopsy approaches may facilitate detection of early stage PDAC when curative treatments can be employed. Design To assess circulating marker discrimination in training, testing and validation patient cohorts (total n=426 patients), plasma markers were measured among PDAC cases and patients with chronic pancreatitis, colorectal cancer (CRC), and healthy controls. Using CA19-9 as an anchor marker, measurements were made of two protein markers (TIMP1, LRG1) and cell-free DNA (cfDNA) pancreas-specific methylation at 9 loci encompassing 61 CpG sites. Results Comparative methylome analysis identified nine loci that were differentially methylated in exocrine pancreas DNA. In the training set (n=124 patients), cfDNA methylation markers distinguished PDAC from healthy and CRC controls. In the testing set of 86 early stage PDAC and 86 matched healthy controls, CA19-9 had an area under the receiver operating characteristic curve (AUC) of 0.88 (95% CI 0.83 to 0.94), which was increased by adding TIMP1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.06), LRG1 (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02) or exocrine pancreas-specific cfDNA methylation markers at nine loci (AUC 0.92; 95% CI 0.88 to 0.96; p=0.02). In the validation set of 40 early stage PDAC and 40 matched healthy controls, a combined panel including CA19-9, TIMP1 and a 9-loci cfDNA methylation panel had greater discrimination (AUC 0.86, 95% CI 0.77 to 0.95) than CA19-9 alone (AUC 0.82; 95% CI 0.72 to 0.92). Conclusion A combined panel of circulating markers including proteins and methylated cfDNA increased discrimination compared with CA19-9 alone for early stage PDAC.