1534 Background: Quality cancer care depends on timely and efficient evaluation of patients to determine next steps in treatment. To support this goal, we implemented a care delivery model where advanced practice providers (APP) were tasked with seeing new patients as an entry into the system, with a goal of completing testing and referrals prior to a subsequent visit with a surgical oncologist. Methods: A retrospective review was performed focusing on four hepatobiliary and pancreatic surgeons and their corresponding APP teams. The APP-First program was deployed in 2021. The purpose was to increase capacity and best prepare the patient’s work-up prior to an appointment with the surgeon to facilitate treatment initiation. We compared NPs during two distinct time periods, before (7/2018-6/2020) and after (7/2022-6/2024) implementation of APP First . The primary outcome, impact on access, was determined by change in the number of NP seen by the group, and the secondary outcomes were number and proportion of patients receiving treatment at our institution. Patients were excluded if time to care was > 180 days or they received non-GI related care. Changes in outcomes of interest before and after implementation of the program were compared by Chi-square with significance set at p = 0.05. Results: A total of 2585 NPs were seen during the study period with 1797 beginning treatment at our facility (69.5%). During the pre-intervention period 1091 NPs were seen by the group, including 277 (25.5%) initially evaluated by an APP. Following the model implementation, 1494 NPs were seen, 915 (61.2%) by an APP and 579 (38.8%) by an MD (p < 0.001). There was no change in percent of NPs choosing to pursue care at our institution (68.7% vs 68.7%, p = 0.970), however after implementation, patients were more likely to be scheduled for operations after their initial visit (11.4% vs 14.3%, p = 0.031). Conclusions: Implementation APP-first led to increased NPs capacity translating into a 36.9% higher volume of NPs seen, without change in patient satisfaction as demonstrated by an unchanged percentage of patients choosing treatment at our institution. The established workflow within this model facilitated expedited care, resulting in higher proportion of patients treated and an increase in the number and proportion of patients receiving surgery. These data support the implementation of delivery of care models leveraging the role of APPs in a well-integrated system, with overall improved capacity, access, and treatment for patients with cancer. Outcomes of APP-First program. FY 19-20 (n,%) FY 23-24 (n,%) p value Total # NP 1,091 1,494 -- NP Distribution APP MD 277 (25.4)814 (74.6) 915 (61.2)579 (38.8) <0.001 Treated Yes No 750 (68.7)341 (31.3) 1026 (68.7)468 (31.3) 0.970 Surgery 124 (11.4) 213 (14.3) 0.031 Chemotherapy 143 (13.1) 194 (13.0) 0.928 Endoscopy 376 (34.5) 466 (31.2) 0.080 Radiation 112 (10.3) 154 (10.3) 0.972

BACKGROUND:Surgical resection is the only curative treatment of gallbladder cancer (GBC). However, the role of oncologic extended resection (OER) in advanced GBC (T3/T4) remains unclear. This study aimed to evaluate the effect of OER in patients with advanced GBC. METHODS:This retrospective, multicenter study analyzed 419 patients diagnosed with GBC at 17 institutions across 7 countries between 1997 and 2022. Adjusted logistic regression was used to examine factors affecting R1 resection and lymph node positivity. Survival was assessed using Kaplan-Meier curves and multivariate Cox proportional hazards. RESULTS:Of the cohort, 369 patients with T3 GBC and 50 patients with T4 GBC were identified. Predictors of R1 status for patients with T3/T4 GBC included jaundice before surgery (odds ratio [OR], 3.03 [95% CI, 1.68-5.45]), perineural and/or lymphovascular invasion (OR, 2.43 [95% CI, 1.35-4.39]), adjacent organ resection (OR, 2.05 [95% CI, 1.09-3.85]), overall morbidity (OR, 1.64 [95% CI, 1.01-2.66]), and lymph node metastasis (OR, 2.69 [95% CI, 1.55-4.66]). Morbidity was higher in patients (64.8%) with T4 GBC than in patients (38.2%) with T3 GBC, with severe morbidity at 46.3% and 17.1%, respectively. Of note, 90-day mortality was 4.1% for patients with T3 GBC and 12% for patients with T4 GBC. The 3-year overall survival rate was 33% for patients with T3 GBC and 4% for patients with T4 GBC (log-rank P <.001). CONCLUSION:Advanced-stage GBC outcomes vary with resection status. OER is associated with increased morbidity, particularly in patients with T4 GBC, for whom survival benefits are limited. Careful patient selection for aggressive surgical treatment is crucial to avoid unnecessary morbidity while carefully weighing the potential survival benefits.

Background: In patients with curatively resected pancreatic adenocarcinoma who have undergone neoadjuvant chemotherapy (NACT), evidence supporting the benefit of additional adjuvant chemotherapy (ACT) remains limited. We aim to identify favorable factors contributing to survival benefits in resected pancreatic adenocarcinoma after NACT. Methods: This is a retrospective cohort study of pancreatic adenocarcinoma patients who underwent NACT followed by curative surgical resection between 2008 and 2023 at a single academic institution. Univariate and multivariable analyses were conducted to identify factors contributing to disease-free survival (DFS) and overall survival (OS). Results: A total of 230 patients with a median age of 68 years (IQR, 62-72 years) were included. All patients underwent curative surgical resection. Of these, 42% received neoadjuvant modified (m) FOLFIRINOX (96/230), 15% received gemcitabine plus nab-paclitaxel (GEM-NAB) (34/230), and 43% received gemcitabine, docetaxel, and capecitabine (GTX) (100/230). In univariate analysis, lower College of American Pathologists (CAP) tumor regression grade (TRG) (0-1 vs. 2-3, median DFS: 29.8 vs. 14.2 months, p = 0.0081) and receipt of ACT (Yes vs. No, median DFS: 22.2 vs. 12.4 months, p < 0.0001) demonstrated significant associations with superior DFS. Multivariable analysis identified receipt of ACT as an independent predictor of superior DFS (HR 0.55, 95% CI: 0.39-0.78, p = 0.0007) and OS (HR 0.49, 95% CI: 0.33-0.71, p = 0.0002). However, the NACT regimen (mFOLFIRINOX vs. GEM-NAB) and the transition between neoadjuvant and adjuvant therapy (de-escalation vs. continuation vs. change) did not correlate with DFS or OS. The duration of perioperative chemotherapy showed a trend toward improved survival outcomes, though not statistically significant (6 months vs. <6 months: DFS, 19.4 vs. 16.2 months, p = 0.1448; OS, 49.6 vs. 30.4 months, p = 0.0623). In the following subgroup analyses, receipt of ACT provided DFS/OS benefits in patients who did not achieve a major pathologic response, pN0, or R0 resection (DFS: p = 0.0003; OS: p < 0.0001). However, it did not provide DFS/OS benefits in those who achieved a major pathologic response with pN0/R0 to NACT (DFS: p = 0.8036; OS: p = 0.1877). Conclusions: In resected pancreatic adenocarcinoma following NACT, receiving ACT was associated with favorable survival outcomes. Additional ACT appears to benefit patients who did not achieve a major pathologic response (pN0 or R0) to neoadjuvant therapy, with limited benefit for those who achieved a major response with pN0/R0. The specific NACT regimen (mFOLFIRINOX vs. GEM-NAB) and changes in ACT from NACT did not significantly influence survival outcomes in our cohort.

PURPOSE This study aimed to assess (1) the prognostic value of circulating tumor DNA (ctDNA) and (2) the ability of ctDNA to detect recurrence compared with standard surveillance in curatively resected early-stage biliary tract cancer (BTC). METHODS This retrospective, multicenter cohort study evaluated serial ctDNA testing for surveillance in patients with early-stage BTC after curative resection. We evaluated the relapse-free survival (RFS) by ctDNA positivity. The sensitivity of ctDNA in detecting a confirmed recurrence of BTC, defined as a biopsy-proven or true progression by radiographic tumor dynamics, was evaluated. The lead time was calculated from the first ctDNA detection to the confirmed recurrence. RESULTS A total of 56 patients with curatively resected stage I-III BTC were included in this study, with a median follow-up of 12.8 months from the date of surgery. ctDNA detection during the molecular residual disease window period (median RFS, 6.6 months v not reached; hazard ratio [HR], 26 [95% CI, 2.6 to 265]; P < .0001) and during the surveillance period (median RFS, 19.3 months v not reached; HR, 20 [95% CI, 2.6 to 153]; P < .0001) were associated with poorer RFS. Sixteen patients had confirmed recurrence. ctDNA identified recurrence in 93.8.% (15/16) of the recurred patients with an average lead time of 3.7 months. Carbohydrate antigen 19-9 levels did not show any significant correlation with RFS (HR, 1.17 [95% Cl, 0.24 to 5.71]; P = .844) in contrast to ctDNA. CONCLUSION The findings from our real-world cohort study revealed the (1) promising value of ctDNA as a prognostic biomarker for relapse in curatively resected BTC and (2) potential early detectability of recurrence by ctDNA compared with standard surveillance.

Cholangiocarcinoma (CCA) is a unifying title granted to epithelial adenocarcinomas specific to the bile ducts making up 10–25

BACKGROUND:Gallbladder cancer (GBC) has a poor prognosis, particularly in advanced stages, with surgery often offering limited survival benefit. This study aimed to identify risk factors for futile surgery (FS), defined as procedures followed by early recurrence or death. METHODS:An international cohort of 788 patients who underwent up-front GBC surgery across 18 centers was analyzed. Futility was defined as recurrence within 5 months or death within 90 days after oncological surgery. A multivariate model was built, and an online calculator was developed to predict the probability of FS. RESULTS:A total of 107 patients (13.6%) experienced FS, with a median survival of only 6.8 months, compared with 57.4 months for nonfutile cases. The key risk factors identified were the T3-T4 tumor stage (odds ratio [OR] 2.20; 95% confidence interval [CI] 1.30-3.71), lymph node involvement (OR 1.91; 95% CI 1.22-2.98), and multivisceral resection (OR 2.25; 95% CI 1.28-3.94). Incidental GBC diagnoses showed a lower risk of FS (OR 0.41; 95% CI 0.25-0.67). The predictive model had a strong discriminative ability (c-statistic: 0.749). Decision curve analysis demonstrated the superiority of the multivariate model over individual predictors. CONCLUSIONS:Refining patient selection can reduce futile surgeries in GBC. The predictive model provides a valuable online tool ( https://aicep.website/?cff-form=25 ) to improve decision-making and outcomes by minimizing unnecessary interventions.

Advanced Practice Provider (APP)-First is a delivery of care model implemented at our institution where APPs see new patients as an entry into the system to complete any missing diagnostic testing prior to appointment with the surgical oncologist. The program’s purpose was to increase capacity, expedite care, and best prepare the patient’s workup to facilitate treatment initiation. A retrospective review was performed focusing on the hepatobiliary and pancreatic surgical team. New patient (NP) volume, percentage of patients electing to receive care at our institution, and treatments received after first visit were evaluated before and after implementation of the program. The primary outcome, impact on access, and the secondary outcomes were number and proportion of patients receiving treatment at our institution. A total of 2585 NPs were seen during the study periods. During the pre-intervention period, 1091 NPs were seen by the group, including 277 (25.5

703 Background: The association between homologous recombination deficiency (HRD) in pancreatic ductal adenocarcinoma (PDAC) and sensitivity to platinum-based chemotherapy highlights the need to further understand how germline DNA repair mutations influence the efficacy of different therapies. Given the recent ALLIANCE data that chemotherapy alone is an acceptable standard of care to enhance R0 resection, the focus has shifted towards the contribution of radiotherapy. However, the relationship between germline DNA repair mutations in general and radiosensitivity remains less understood. This study explores the relationship between germline mutations and the Radiosensitivity Index (RSI) gene signature. Methods: After obtaining institutional review board approval, a retrospective analysis was performed of patients who had both RSI and germline mutation testing (i.e., BRCA1, BRCA2, BLM, ATM, MLH1, MSH2, MSH6, PMS2, and BARD mutations) between 1999 and 2023 at a single institution. Student T, Chi squared, Kaplan Meier (KM), Cox univariate log regression (UVA), and Mann-Whitney U (MWU) tests were used for statistical analyses. Results: A total of 25 patients were included, 13 with mutations and 12 without. MWU analysis demonstrated a significant difference in RSI values, where patients with mutations exhibited greater radiosensitivity (mean 0.379 vs. 0.464, p=0.040). The median age at diagnosis, max diameter of tumor, and baseline CA 19-9 were 67 years (range 47 – 77), 3.4 cm (range 0.8 – 8.2), and 288 (9.5 – 26,100), respectively. Most of the tumors were resectable (84%), stage IIB (36%), and grade 2 (68%). All patients underwent resection, with the majority without neoadjuvant therapy (96%). Most patients received chemotherapy (n=18; 72%), most commonly gemcitabine monotherapy (n=14/18). A majority also received radiation therapy (n=15; 60%), with 93% receiving chemoradiation (n=14/15). The median follow-up was 20.8 months. KM analysis yielded a median overall survival (OS) of 20.0 months (95% CI: 7.1-33.0) and progression-free survival (PFS) of 15.1 months (95% CI: 12.3-18.0) for the entire cohort. At the time of analysis, 15.4% of patients with mutations were alive (>10 years), compared to none without mutations (p=0.157). There were no statistically significant differences between the two cohorts for clinical outcomes on KM analysis. On UVA, worse OS was correlated with stage III (HR 7.9, 95% CI 1.2 – 50.2) and IV (HR 11.8, 95% CI 1.4 – 102.3). No other variables were associated with OS on UVA or on mutant-only subgroup analysis. Conclusions: Our findings demonstrate an increased radiosensitivity in patients with germline DNA repair mutations, suggesting these cancers might be more susceptible to radiation-induced DNA damage. Since our results are constrained by the small sample size, further studies are needed to understand the relationship between PDAC with DNA repair mutations.

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Surgical resection is the most reliable chance for cure, but high rates of positive margins and local failure persist. Neoadjuvant therapies (NAT), including chemotherapy and radiation therapy (RT), are being explored to improve surgical outcomes, particularly in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). This review aims to summarize the current landscape and future directions for neoadjuvant RT (NART) in PDAC. Methods: The review includes a detailed analysis of past and ongoing clinical trials investigating various NART approaches in PDAC, with an emphasis on different RT techniques, fractionation schemes, and their integration into multimodal treatment strategies. Results: Early evidence suggests that NART can improve resection margins and local control. However, recent trials, including the Alliance A021501 and LAP-07 trials, have failed to demonstrate significant survival benefits with the addition of RT to NAT. Nevertheless, nuances in trial design and execution continue to keep the question of NART open. Newer approaches, such as stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), show promise in improving local control and survival, but further phase 3 trials are needed. Conclusions: While NART has shown potential in improving local control in PDAC, its impact on overall survival remains unclear. Ongoing trials, particularly those utilizing advanced techniques like SMART, are critical in defining the role of RT in the neoadjuvant setting for PDAC. Collaboration across multidisciplinary teams is essential to optimize treatment strategies and trial outcomes.

Pancreaticoduodenectomy, first described in 1935, has subsequently been refined over decades into the operation performed today for tumors of the pancreatic head and periampullary region. For years following Whipple's first publication, tumors found to be inseparable from the surrounding vasculature were considered locoregionally advanced and unresectable. Fortner began performing regional pancreatectomy with routine enbloc resection of the portal vein/superior mesenteric vein in an attempt to address high local recurrence rates and high rates of aborted operations due to vascular involvement.