Background/Objectives: Stereotactic body radiotherapy (SBRT) aims to prolong overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC) with vascular contact without progression of disease after (m)FOLFIRINOX. The primary objective of this study was to determine the potential value of SBRT. Methods: This nationwide, retrospective cohort study included patients with PDAC without progression of disease after at least four cycles of (m)FOLFIRINOX. The study comprised two cohorts, the SBRT and the No SBRT group. A landmark analysis excluded patients with a follow-up or OS time less than 12 months to minimize immortal time bias in the SBRT group. The primary outcome was OS from diagnosis. Secondary outcomes were the histopathological characteristics after resection. Results: Overall, 331 patients were included, of whom 231 were in the landmark analysis. In the overall cohort, the median OS was 20.7 months in the SBRT group versus 15.7 months in the No SBRT group (p = 0.004). In the landmark analysis, the median OS was 23.2 months in the SBRT group compared to 22.3 months in the No SBRT group (p = 0.554). These results indicate the presence of immortal time bias in the overall cohort in favor of the SBRT group. In the subgroup after resection, ypT0-2 (95% versus 76.5% [p = 0.026]), ypN0 (75% versus 37.3% [p < 0.004]), and absence of perineural invasion (50% versus 68.6% [p = 0.015]) were more prevalent in the SBRT group. Conclusions: In a landmark analysis, including only patients who survived at least 12 months after diagnosis, we found no difference in median OS between (m)FOLFIRINOX-only and (m)FOLFIRINOX with consecutive SBRT.

The incidence of pancreatic ductal adenocarcinoma (PDAC) is constantly increasing. Surgical resection, in combination with systemic chemotherapy, offers the only option for long-term survival or even cure. However, the high toxicity rates of modern and most-effective chemotherapy protocols limit this treatment option to patients with good performance status (PS). Consequently, the Eastern Cooperative Oncology Group (ECOG) performance score is essential for selecting treatment protocols. In addition, the perioperative complications and survival rates of patients with a reduced PS undergoing surgery for PDAC are unclear. This study aims to evaluate the perioperative morbidity and mortality rates in patients with a reduced PS (ECOG ≥ 2) after resection of PDAC as well as disease-free (DFS) and overall survival (OS). This is a pan-European and African retrospective study conducted at participating centers represented by members of the European–African Hepato-Pancreato-Biliary Association (E-AHPBA). This study will include all consecutive patients with ECOG PS ≥ 2 who underwent pancreatic surgery for PDAC between January 1, 2015, and December 31, 2024. Participating centers enter data via an electronic case report form on REDCap® (Vanderbilt University, Tennessee). The primary outcomes are perioperative morbidity and mortality rates, DFS, and OS. The secondary objectives are related to the type of chemotherapy regimens applied. Impaired PS may negatively affect surgical and oncological treatment algorithms and outcomes. This multicenter study will help to understand how patients with PDAC and ECOG PS ≥ 2 are treated in daily clinical practice throughout Europe and Africa. The results of this large patient cohort analysis are expected to identify the best treatment algorithm for this patient group.

INTRODUCTION:Socialdeprivation, which is exaggerated by lower household income, shortens life expectancy and worsens cancer survival. In pancreatic adenocarcinoma, novel treatment strategies aim to extend survival and centralization of care has increased distance to hospital. The effect of distance to hospital and different treatment regimens on survival stratified by household income remains unexplored. METHODS:A nationwide retrospective study using Netherlands Cancer Registry data (2017-2022) included patients with localized pancreatic adenocarcinoma. Patients were categorized into three groups based on household income (lowest, intermediate and highest income) and two distance groups based on median distance to hospital. Multivariable logistic and Cox regression analyses assessed the effect of lower household income and distance on treatment and survival. Kaplan-Meier curves were used for univariable survival analysis. RESULTS:Among 5926 patients, individuals from lower household income received less anti-cancer treatment (44% lowest vs. 63% highest, P < 0.001). Living within 14 km increased the likelihood of resection (Odds ratio (OR) 1.44, 95%CI 1.28-1.63, P < 0.001) and adjuvant chemotherapy (OR 1.29, 95%CI 1.18-1.71, P < 0.001). Median survival was 7 months (lowest income), 9 months (intermediate), and 11 months (highest income) (P < 0.001). In the multivariable analysis, worse survival in the lowest income group persisted after case-mix adjustment (HR (highest vs lowest): 0.92, 95% CI 0.86-0.98, P < 0.001). However, after additional adjustment for treatment differences, survival differences between income groups disappeared (P = 0.180). CONCLUSION:Lower household income negatively impacts the likelihood of receiving treatment for patients with pancreatic adenocarcinoma. Additionally, distance to hospital is negatively associated with the probability of receiving resection and subsequent treatment.

Abstract Background The introduction of (m)FOLFIRINOX and gemcitabine-nab-paclitaxel has changed the perspective for patients with locally advanced pancreatic cancer (LAPC). Consequently, in experienced centres 23% of patients with LAPC undergo a resection with 5-year overall survival (OS) rates of up to 25%. In the Netherlands, the nationwide resection rate for LAPC remains low at 8%. The PREOPANC-4 program aims for a nationwide implementation of the international multidisciplinary best-practice to improve patient outcome. Methods Nationwide program implementing the international multidisciplinary best-practice for LAPC. In the training phase, multidisciplinary and surgical webinars are given by 4 international experts, leading to a clinical protocol, followed by surgical off-site and on-site proctoring sessions. In the implementation phase, the clinical protocol will be implemented in all centres, including a nationwide expert panel (2022–2024). Healthcare professionals will be trained in shared decision-making. Consecutive patients diagnosed with pathology-proven LAPC (i.e., arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion [DPCG criteria]) are eligible. Primary outcomes are median and 5-year OS from diagnosis, resection rate, in-hospital/30-day mortality and major morbidity (i.e., Clavien-Dindo grade ≥ IIIa), and radical resection (R0) rate. Secondary outcomes include quality of life, functioning, side effects, and patients’ healthcare satisfaction in all included patients. Outcomes will be compared with patients with borderline resectable pancreatic cancer (BRPC) treated with neoadjuvant FOLFIRINOX in the PREOPANC-2 trial (EudraCT: 2017–002036-17) and a historical cohort of patients with LAPC from the PACAP registry (NCT03513705). The existing prospective LAPC Registry and PACAP PROMs (NCT03513705) will be used for data collection. In qualitative interviews, treatment preferences, values, and experiences of LAPC patients, their relatives, and healthcare professionals will be assessed for the development of shared decision-making supportive tools. It is hypothesized that the program will double the nationwide LAPC resection rate to 16% with major morbidity < 50% and mortality ≤ 5%, and OS following resection similar to that observed in patients with BRPC. Discussion The PREOPANC-4 program aims to safely implement the international multidisciplinary best-practice for LAPC leading to benchmark outcomes for both short-term morbidity, mortality, and OS. Trial registration PREOPANC-4 program was registered at ClinicalTrials.gov (NCT05524090) on September 1, 2022.

BACKGROUND:Guidelines recommend a time to adjuvant chemotherapy (TTC) within 12 weeks after pancreatic ductal adenocarcinoma (PDAC) resection. The aim of this study to evaluate the association between TTC and clinical outcomes in patients undergoing PDAC resection in the Netherlands. METHODS:Patients undergoing upfront, macroscopically radical PDAC resection (2014-2019) in the Netherlands were included. Patients were stratified into receiving no adjuvant chemotherapy, TTC 0-6 weeks, TTC 6-12 weeks, and TTC ≥12 weeks. Multivariable cox and logistic regression analyses were used to assess the association between TTC and overall survival (OS), and between TTC and adjuvant chemotherapy completion. RESULTS:Of 1459 patients, 543 (37 %) did not receive adjuvant chemotherapy, while TTC was 0-6 weeks in 245 (17 %), 6-12 weeks in 612 (42 %), and ≥12 weeks in 59 (4 %) patients. TTC in weeks (HR 0.99, 95 %CI 0.97-1.01, P = 0.39) and different TTC groups were not associated with OS (TTC 6-12 weeks vs TTC 0-6 weeks: HR 1.06, 95 %CI 0.76-1.49, P = 0.72, TTC ≥12 weeks vs TTC 0-6 weeks: (HR 0.62, 95 %CI 0.32-1.21, P = 0.16). Adjuvant chemotherapy completion was associated with improved OS (HR 0.81, 95 %CI 0.51-0.98, P = 0.04). Compared to TTC 0-6 weeks, TTC 6-12 weeks was associated with adjuvant chemotherapy completion (OR 1.57, 95 %CI 1.33-1.84, P < 0.001), while TTC ≥12 weeks was not (OR 1.13, 95 %CI 0.85-1.51, P = 0.39). CONCLUSION:TTC in patients with upfront PDAC resection was not associated with survival, but TTC 6-12 weeks was associated with adjuvant chemotherapy completion. These findings support prioritizing postoperative recovery rather than pushing early adjuvant chemotherapy initiation.

IntroductionSex and gender are modulators of health and disease and may have impact on treatment allocation and survival in patients with cancer. In this study, we analyzed the impact of sex and gender on treatment allocation and overall survival in patients with stage I-III pancreatic cancer.MethodsPatients with stage I-III pancreatic cancer diagnosed between 2015 and 2020 were selected from the nationwide Netherlands Cancer Registry. Associations between sex and gender and the probability of receiving surgical and/or systemic treatment were examined with multivariable logistic regression analyses. Overall survival was assessed with log rank test and multivariable Cox proportional hazard analysis.ResultsAmong 6855 patients, 51.2% were female. Multivariable logistic regression analyses with adjustment for known confounders (age, performance status, comorbidities, tumor location, tumor stage and previous malignancies) showed that females less often received systemic chemotherapy compared to males (OR 0.799, 95%CI 0.703-0.909, p<.001). No difference was found in the probability for undergoing surgical resection. Furthermore, females had worse overall survival compared to males (median OS 8.5 and 9.2 months respectively, 95%CI 8.669-9.731).ConclusionThis nationwide study found that female patients with stage I-III pancreatic cancer significantly less often received systemic treatment and had worse overall survival as compared to males. Disparities in pancreatic cancer care can be decreased by recognizing and resolving potential obstacles or biases in treatment decision-making.

BACKGROUND:Patients with localized (that is non-metastatic) pancreatic ductal adenocarcinoma with an inadequate response or toxicity to first-line chemotherapy may benefit from chemotherapy switch. The aim was to explore the available data on the use and effect of chemotherapy switch, as reported in the literature. METHODS:A systematic search was conducted in Embase, MEDLINE (Ovid), the Web of Science, Cochrane, and Google Scholar on 1 December 2023. The main outcomes were the proportion of patients who underwent chemotherapy switch and the carbohydrate antigen 19-9 response and resection, R0 resection, and ypN0 resection rates after chemotherapy switch. Data were pooled using a random-effects model. RESULTS:A total of five retrospective studies, representing 863 patients with localized pancreatic ductal adenocarcinoma, were included and 226 of the 863 patients underwent chemotherapy switch. In four studies, first-line chemotherapy consisted of 5-fluorouracil/leucovorin/irinotecan with oxaliplatin ('FOLFIRINOX') and patients were switched to gemcitabine with nab-paclitaxel. Reasons for chemotherapy switch included an inadequate biochemical, clinical, or radiological response, or toxicity. Three studies compared patients who underwent chemotherapy switch with patients who only received first-line chemotherapy and found that the proportion of patients who underwent chemotherapy switch was 20.5% (95% c.i. 10.5% to 36.3%). The pooled resection rate after chemotherapy switch was 42.0% (95% c.i. 16.6% to 72.5%). Two studies compared the chance of resection after chemotherapy switch versus first-line chemotherapy alone and found a risk ratio of 0.88 (95% c.i. 0.65 to 1.18). Two studies, with a combined total of 576 patients, found similar postoperative survival for patients who underwent chemotherapy switch and patients who only received first-line chemotherapy. CONCLUSION:One in five patients with localized pancreatic ductal adenocarcinoma underwent chemotherapy switch after an inadequate response or toxicity to first-line chemotherapy. The pooled resection rate after chemotherapy switch was 42% and similar in overall survival compared with first-line chemotherapy only. Three ongoing trials are investigating chemotherapy switch in patients with an inadequate radiological or carbohydrate antigen 19-9 response.

Purpose: Pancreatic neuroendocrine tumors (pNET) represent only 6% of pancreatic tumors, compared to 93% for pancreatic ductal adenocarcinoma (PDAC). Surgical management is similar; however it is assumed that patients with pNET show worse operative outcomes. Ideal Outcome is a composite outcome measure that reflects the hospital's surgical performance as well as quality of current practice. The aim of this study was to compare Ideal Outcome of pancreatic resections for pNET to PDAC in order to gain insight on potential improvements of pNET surgery. Method: This observational cohort study included all consecutive patients who underwent pancreatoduodenectomy (PD) or distal pancreatectomy (DP) for pNET or PDAC in all 19 centers in the mandatory nationwide Dutch Pancreatic Cancer Audit (2014 – 2021). The primary outcome was Ideal outcome; defined as the absence of major complications (Clavien-Dindo grade ≥3, excluding POPF), POPF grade B/C, prolonged length of stay (≥75th percentile), readmissions, and postoperative mortality. Results: This study included 3,375 patients who underwent a pancreatic resection (524 pNET vs 2,851 PDAC). Ideal outcome occurred less often after pNET-surgery (47.7% vs 55.7%, p<0.001). This difference was only present after PD (n=212) (37.7% vs 56.3%, p<0.001) and not for DP (n=312) (54.5% vs 52.5%, p=0.60). Of the individual components of Ideal outcome, POPF showed the most difference between pNET and PDAC patients (32.1 versus 7.9%, p<0.001). A BMI ≥25 kg/m2 and multivisceral resection was associated with a lower Ideal Outcome rate after PD for pNET (OR 0.36 [95% CI 0.19 – 0.70], p=0.002 and 0.26 [0.08 – 0.83], p=0.023, respectively). Conclusion: Patients undergoing PD for pNET have a significantly lower Ideal Outcome rate compared to patients with PDAC, predominantly due to the difference in POPF. Risk factors are possibly more prevalent and preventive factors should be evaluated for patients with pNET. These outcomes can be valuable in the preoperative treatment planning, since non-operative measures should be weighed against these surgical complication rates.