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Prospective Memory (PM) is the ability to encode an intention in memory and retrieve it at the right time in the future. After the intention is formed, it must be maintained in memory while simultaneously monitoring the environment until the occurrence of the stimulus associated with its retrieval. Therefore, monitoring and maintenance processes must work in conjunction to subserve PM processing (monitoring/maintenance phase). Several brain regions play a role in PM, such as the anterior prefrontal cortex, inferior parietal lobules, and precuneus. Notably, these regions belong to different brain networks and are differently involved depending on the memory and attentional requests of the PM task. In this study, we investigate the neural bases of PM from a network perspective, using functional connectivity (FC) analysis to identify the networks involved in the attentional and memory mechanisms underlying PM. To this end, we analyzed MEG data collected in two different PM conditions, enhancing either the monitoring (i.e., attention) or the maintenance (i.e., memory) loads of the PM task. To disentangle the neural correlates of these mechanisms from other processes occurring after stimulus presentation, the analysis focused on the prestimulus time window (monitoring/maintenance phase). The monitoring-load condition was characterized by increased inter-network FC of the Dorsal Attention Network (DAN) in the alpha band, a marker of increased top-down monitoring. In contrast, the maintenance-load condition was associated with increased connectivity of the Ventral Attention Network (VAN) with the FrontoParietal Control and the Default-Mode Networks (FPCN and DMN, respectively). Additionally, response times were found to correlate with prestimulus alpha connectivity of different networks in the two conditions. These differences in connectivity within and between networks support the hypothesis that different networks (DAN, or VAN and DMN) and mechanisms (top-down or bottom-up, respectively) are involved in PM processing depending on the features of the PM task., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Vicentin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim: To validate the prognostic value of the PAncreatic NeoAdjuvant MAssachusetts (PANAMA)-score and to determine its predictive ability for survival benefit derived from adjuvant treatment in patients after resection of pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant FOLFIRINOX., Background: The PANAMA-score was developed to guide prognostication in patients after neoadjuvant therapy and resection for PDAC. As this score focuses on the risk for residual disease after resection, it might also be able to select patients who benefit from adjuvant after neoadjuvant therapy., Methods: This retrospective international multicenter study is endorsed by the European-African Hepato-Pancreato-Biliary Association (E-AHPBA). Patients with PDAC who underwent resection after neoadjuvant FOLFIRINOX were included. Mantel-Cox regression with interaction analysis was performed to assess the impact of adjuvant chemotherapy., Results: Overall, 383 patients after resection of PDAC following neoadjuvant FOLFIRINOX were included of whom 187 (49%), 137 (36%), and 59 (15%) had a low-risk, intermediate-risk, and high-risk PANAMA-score, respectively. A discrimination in median OS was observed stratified by risk groups (48.5, 27.6, and 22.3 months, Log-Rank-Plow-intermediate=0.004, Log-Rank-Pintermediate-high=0.027). Adjuvant therapy was not associated with an OS difference in the low-risk group (HR 1.50, 95%CI:0.92-2.50), whereas improved OS was observed in the intermediate (HR 0.58, 95%CI:0.34-0.97) and high-risk groups (HR 0.47, 95%CI:0.24-0.94) (p-interaction=0.008)., Conclusions: The PANAMA 3-tier risk groups (low-risk, intermediate-risk, and high-risk, available via pancreascalculator.com) correspond with differential survival in patients with resected PDAC following neoadjuvant FOLFIRINOX. The risk groups also differentiate between survival benefit associated with adjuvant treatment, with only the intermediate- and high-risk groups associated with improved OS., Competing Interests: Conflicts of Interest: Marco del Chiaro has been awarded an industry grant (Haemonics, Inc.) to conduct a multicenter study to evaluate the prognostic implications of TEG in pancreatic caner. Marco del Chiaro is co-principal investigator of a Boston Scientific sponsored international multicenter study on the use of intraoperative pancreatoscopy of patients with IPMN. All other authors report no relevant conflicts of interest., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: The effect of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) chemotherapy on overall survival (OS) is unclear because current studies do not account for the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen., Objective: To investigate the association of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX with OS, taking into account the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen., Design, Setting, and Participants: This retrospective cohort study included patients with localized pancreatic adenocarcinoma treated with 2 to 11 cycles of preoperative (m)FOLFIRINOX followed by resection across 48 centers in 20 countries from 2010 to 2018. Patients who died within 3 months after surgery were excluded (landmark). Data were analyzed from February 1 to December 31, 2023., Exposures: Preoperative (m)FOLFIRINOX chemotherapy followed by resection and eventually followed by adjuvant chemotherapy., Main Outcomes and Measures: The primary outcome was OS, calculated from the 3-month landmark. Cox regression analysis, including interaction analyses, was performed to investigate the association of adjuvant chemotherapy with OS., Results: Overall, 767 patients were included after resection of pancreatic adenocarcinoma (median [IQR] age, 62 [55-67] years; 404 [52.7%] male). Adjuvant chemotherapy was independently associated with prolonged OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87), confirmed by adjusted OS curves. The interaction analysis to assess estimated treatment effect across subgroups was not statistically significant. The forest plot and interaction test suggest that the association of adjuvant chemotherapy was lower among patients receiving 8 or more cycles of preoperative (m)FOLFIRINOX, those who had radiological response, and those with ypN0 disease. Compared to no adjuvant chemotherapy, both adjuvant (m)FOLFIRINOX (HR, 0.57; 95% CI, 0.40-0.80) and other multiagent adjuvant regimens (HR, 0.61; 95% CI, 0.41-0.92) were associated with prolonged OS, whereas single-agent adjuvant chemotherapy was not (HR, 0.75; 95% CI, 0.55-1.03)., Conclusions and Relevance: In this cohort study, adjuvant (m)FOLFIRINOX and other multiagent chemotherapy regimens were associated with improved OS following resection of localized pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX, whereas single-agent adjuvant chemotherapy was not. The impact of adjuvant chemotherapy on OS may be lower in subgroups such as patients with 8 or more preoperative cycles of (m)FOLFIRINOX, those having radiological response, and those with ypN0.