BackgroundThe role of neoadjuvant chemotherapy (NAT) in patients with resectable pancreatic cancer is being studied in ongoing multicenter randomized trials. The primary aim of this study is to compare survival between NAT and up-front surgery (UFS) in a non-selected population of patients presenting with resectable cancer of the head of the pancreas. Patient and tumor-related factors impacting receipt of NAT and survival were also analyzed.MethodsA single institution prospective database was queried to identify patients who underwent pancreaticoduodenectomy for resectable pancreatic adenocarcinoma from 2019 to 2023. Patient demographic and clinical oncologic factors were compared between those who received NAT and those who underwent UFS. Area Deprivation Index (ADI) and distance traveled were used as surrogate indicators for socioeconomic disparity and rurality, respectively. Overall survival was compared using Kaplan-Meier and Cox Regression analyses.ResultsOf the 83 patients included, one third received NAT. There was no significant difference in 1 yr, 3 yr, or overall survival between patients who received NAT vs up-front surgery. ADI and distance traveled did not impact whether a patient received NAT or survival. On Multivariate Cox Regression analysis, age and performance status were the only factors significantly associated with survival.ConclusionsThere was no significant difference in early mortality and overall survival between NAT and UFS groups.

Neoadjuvant therapy (NT) is increasingly used for patients with pancreatic ductal adenocarcinoma (PDAC). Disease progression, toxicity, and failure to undergo surgical resection are common during NT, yet little research has focused on efforts to optimize care delivery. We sought to define and validate a novel composite outcomes metric that characterizes the successful delivery of NT.

All patients with localized PDAC receiving NT in an intention-to-treat fashion between 2018 and 2023 were retrospectively evaluated. A textbook neoadjuvant experience (TNE) was defined as the absence of mortality, disease progression, or hospital admission during NT as well as the completion of all intended NT and successful surgical resection.

Among 306 patients with localized PDAC, the median age was 66 years and 58.5% were men. Overall, only 85 (28%) experienced a TNE which was more common among patients with potentially resectable (45 of 96, 47%) than borderline resectable (33 of 112, 29%) or locally advanced (7 of 98, 7%) disease. Patients with a TNE experienced greater overall survival than those individuals without a TNE (median not reached vs 16.4 months [95% CI 14.9 to 17.9 months], p < 0.001). On multivariable Cox regression analysis, a TNE was the strongest predictor of improved overall survival (hazard ratio 0.33, 95% CI 0.20 to 0.54, p < 0.001).

A TNE is infrequently achieved among patients with PDAC undergoing NT but is significantly associated with improved long-term outcomes. Future research aimed at optimizing outcomes of NT delivery should incorporate this novel composite metric that may more accurately reflect patient and provider expectations of treatment.

Neoadjuvant therapy (NT) is an increasingly used treatment strategy for patients with localized pancreatic ductal adenocarcinoma (PDAC). Little research has been conducted on cancer care delivery during NT, and the standards for optimal delivery of NT have not been defined.

To develop consensus best practices for delivering NT to patients with localized PDAC.

This study used a modified Delphi approach consisting of 2 rounds of voting, and a series of virtual conferences (from October to December 2023) to reach expert consensus on candidate best practice statements generated from a systematic review of the literature and expert opinion. An interdisciplinary panel was formed including 47 North American experts from surgical, medical, and radiation oncology, radiology, pathology, gastroenterology, integrative oncology, anesthesia, pharmacy, nursing, cancer care delivery research, and nutrition as well as patient and caregiver stakeholders.

Statements that reached 75% agreement or greater were included in final consensus statements.

Of the 47 participating panel members, 27 (57.64%) were male, and the mean (SD) age was 47.6 (8.2) years. Physicians reported completing training a mean (SD) 14.6 (8.6) years prior and seeing a mean (SD) 110.6 (38.4) patients with PDAC annually; 35 (77.7%) were in academic practice. Final consensus was reached on 82 best practices for delivering NT. Of these, 38 statements focused on pre-NT practices, including diagnosis and staging (n = 15), evaluation and optimization (n = 20), and decision-making (n = 3); 29 statements defined best practices during NT, including initiation (n = 3), delivery of therapy (n = 8), restaging practices (n = 12), and management of complications during NT (n = 6); and 15 best practices were identified to guide treatment post-NT, focusing on surgery (n = 7), pathology (n = 4), and follow-up (n = 3).

Using a modified Delphi consensus technique, best practice guidelines were developed focusing on the optimal standards for delivering NT to patients with localized PDAC. Given the prognostic importance of completing multimodality therapy, efforts to standardize and optimize the delivery of NT represent an immediate opportunity to decrease care variation and improve outcomes for patients with PDAC. Future research should focus on validating and implementing best practice standards into clinical practice.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, and the most common cause of cancer-related deaths. In the past, vascular infiltration of the tumor rendered the disease unresectable. However, today, venous or arterial involvement of a PDAC is classified as borderline resectable (BR) or locally advanced (LA) disease. Pancreaticoduodenectomy (PD) with vascular resections is a promising intervention intended for complete resection of BR- and LA-PDAC. This study aims to assess the overall survival of patients undergoing PD with vascular resections, compared to those without. A PubMed search was conducted for cohort studies that included patients with BR- or LA-PDAC treated with vascular resections. The retrieved publications were screened following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. The study protocol was registered at the International Prospective Register for Systematic Reviews (PROSPERO). Sixteen cohort studies were included in our systematic review. Fourteen of them included patients undergoing PD with venous-only resections for PDAC. The 5-year overall survival rates ranged from 8.0% to 22.2% for vascular resection patients, and 4.0% to 24.3% for standard PD patients. Three cohorts included patients with PDAC and arterial and/or venous involvement who were treated with arterial resections. Their median overall survival ranged from 13.7 to 17.0 months, similar to that of patients who did not undergo vascular resections. PD with vascular resections in patients with BR- and LA-PDAC could lead to similar overall survival to that after standard PD.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited effective therapeutic options. Due to a variety of cancer cell-intrinsic factors, including KRAS mutations, chemokine production, and other mechanisms that elicit a dysregulated host immune response, PDAC is often characterized by poor immune infiltration and an immune-privileged fibrotic stroma. As understanding of the tumor microenvironment (TME) evolves, novel therapies are being developed to target immunosuppressive mechanisms. Immune checkpoint inhibitors have limited efficacy when used alone or with radiation. Combinations of immune therapies, along with chemotherapy or chemoradiation, have demonstrated promise in preclinical and early clinical trials. Despite dismal response rates for immunotherapy for metastatic PDAC, response rates with neoadjuvant immunotherapy are somewhat encouraging, suggesting that incorporation of immunotherapy in the treatment of PDAC should be earlier in the disease course. Precision therapy for PDAC may be informed by advances in transcriptomic sequencing that can identify immunophenotypes, allowing for more appropriate treatment selection for each individual patient. Personalized and antigen-specific therapies are an increasing topic of interest, including adjuvant immunotherapy using personalized mRNA vaccines to prevent recurrence. Further development of personalized immune therapies will need to balance precision with generalizability and cost.

Venous thromboembolism (VTE) remains a persistent source of postoperative morbidity despite prevention and mitigation efforts. Cancer, surgery, and chemotherapy are known risk factors for VTE. Existing literature suggests that neoadjuvant therapy (NAT) may contribute to increased VTE risk in the postoperative period, but few authors specifically examine this relationship in distal pancreatic adenocarcinoma (PDAC). In this study, we analyze the association of NAT and postoperative VTE in patients who underwent distal pancreatectomy (DP) for PDAC.

Using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database, we analyzed the Procedure Targeted files for pancreatectomy from 2014 to 2020. Adults with PDAC who underwent DP were grouped by receipt of NAT. The primary outcome was the rate of deep venous thrombosis (DVT) and the secondary outcome was the rate of pulmonary embolism (PE). We performed univariate and multivariate logistic regression analysis to determine risk factors associated with postoperative DVT.

There were 4327 patients with PDAC who underwent DP. Of these, 1414 (32.7%) had NAT. Receipt of NAT was significantly associated with postoperative DVT requiring therapy (3.5% vs. 2.3%, p = 0.02), but was not associated with PE (p = 0.42). On MVA, NAT was associated with a 73% greater chance of developing postoperative DVT [odds ratio (OR) 1.73, 95% CI 1.18-2.55].

Patients who receive NAT prior to DP for PDAC are 73% more likely to develop postoperative DVT compared with upfront resection. As NAT becomes more commonplace, these high-risk patients should be prioritized for guideline-recommended extended duration prophylaxis.

Surgical resection combined with systemic chemotherapy is the cornerstone of treatment for patients with localized pancreatic cancer. Upfront surgery is considered suboptimal in cases with extensive vascular involvement, which can be classified as either borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In these patients, FOLFIRINOX or gemcitabine plus nab-paclitaxel chemotherapy is currently used as preoperative chemotherapy and is eventually combined with radiotherapy. Thus, more patients might reach 5-year overall survival. Patient selection for chemotherapy, radiotherapy and subsequent surgery is based on anatomical, biological and conditional parameters. Current guidelines and clinical practices vary considerably regarding preoperative chemotherapy and radiotherapy, response evaluation, and indications for surgery. In this Review, we provide an overview of the clinical evidence regarding disease staging, preoperative therapy, response evaluation and surgery in patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer. In addition, a clinical work-up is proposed based on the available evidence and guidelines. We identify knowledge gaps and outline a proposed research agenda.

The historical standard of care in treating operable pancreatic cancer via upfront surgery has been challenged recently using a neoadjuvant approach. The aim of the study is to examine the national practice patterns in the management of pancreatic cancer with an emphasis on the trends of neoadjuvant systemic therapy use.

This is a cross-sectional time-series study using the National Cancer Database from 2006 to 2019. Patients who underwent resection for stage I-II pancreatic adenocarcinoma were selected.

Overall, 25% of patients had neoadjuvant chemotherapy, 49% had surgery followed by adjuvant chemotherapy and 26% had surgery alone. The rate of neoadjuvant chemotherapy has increased from 11% in 2006 to 43% in 2019. There was a decrease in the rate of surgery followed by chemotherapy from 48% to 38%, and a decrease in the rate of surgery alone from 41% to 19%. The rate of radiation therapy use has decreased over time, as has the resection rate, while median overall survival has steadily improved over the years.

In 2019, the rate of using neoadjuvant systemic therapy overtook the rate of surgery first followed by adjuvant systemic therapy, marking a pragmatic national shift in the clinical management of pancreatic cancer.

Matrix metalloproteinases (MMPs) play an essential role in various physiological events. Recent studies have revealed its carcinogenic effect in malignancies. However, the different expression patterns, prognostic value, and immunological value of MMPs in pancreatic ductal adenocarcinoma (PDAC) are yet to be comprehensively explored. We utilized Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus databases to explore the abnormal expression of MMPs in PDAC. Then, Kaplan-Meier survival curve and Cox regression analysis were performed to assess the prognostic value of MMPs. Association between MMPs expression and clinicopathological features was analyzed through UALCAN website. Functional annotations and GSEA analysis were performed to excavate the possible signaling pathways involving prognostic-related MMP. TIMER and TISCH database were used to performed immune infiltration analysis. The expression of prognostic-related MMP in pancreatic cancer cell lines and normal pancreatic cells was detected by Real time quantitative PCR. We observed that 10 MMP genes were consistently up-regulated in GEPIA and GSE62452 dataset. Among them, five highly expressed MMPs (MMP1, MMP3, MMP11, MMP14, MMP28) were closely related to poor clinical outcomes of PDAC patients. Cox regression analysis indicated MMP28 was a risk factor influencing the overall survival of patients. In the clinicopathological analysis, up-regulated MMP28 was significantly associated with higher tumor grade and the mutation status of TP53. GSEA analysis demonstrated that high expression of MMP28 was involved in "interferon_alpha_response" and "P53_pathway". Immune infiltration analysis showed that there was no correlation between MMP28 expression and immune cell infiltration. Single-cell sequencing analysis showed MMP28 has strong correlations with malignant cells and stromal cells infiltration in the tumor microenvironment. And MMP28 was highly expressed in various pancreatic cancer cell lines. In conclusion, MMP28 may represent a potential prognosis biomarker and novel therapeutic molecular targets for PDAC.

Examine the potential benefit of total pancreatectomy (TP) as an alternative to pancreatoduodenectomy (PD) in patients at high risk for postoperative pancreatic fistula (POPF).

TP is mentioned as an alternative to PD in patients at high risk for POPF, but a systematic review is lacking.

Systematic review and meta-analyses using Pubmed, Embase (Ovid), and Cochrane Library to identify studies published up to October 2022, comparing elective single-stage TP for any indication versus PD in patients at high risk for POPF. The primary endpoint was short-term mortality. Secondary endpoints were major morbidity (i.e., Clavien-Dindo grade ≥IIIa) on the short-term and quality of life.

After screening 1212 unique records, five studies with 707 patients (334 TP and 373 high-risk PD) met the eligibility criteria, comprising one randomized controlled trial and four observational studies. The 90-day mortality after TP and PD did not differ (6.3% vs. 6.2%; RR=1.04 [95%CI 0.56-1.93]). Major morbidity rate was lower after TP compared to PD (26.7% vs. 38.3%; RR=0.65 [95%CI 0.48-0.89]), but no significance was seen in matched/randomized studies (29.0% vs. 36.9%; RR = 0.73 [95%CI 0.48-1.10]). Two studies investigated quality of life (EORTC QLQ-C30) at a median of 30-52 months, demonstrating comparable global health status after TP and PD (77% [±15] vs. 76% [±20]; P =0.857).

This systematic review and meta-analysis found no reduction in short-term mortality and major morbidity after TP as compared to PD in patients at high risk for POPF. However, if TP is used as a bail-out procedure, the comparable long-term quality of life is reassuring.

Neoadjuvant therapy (NT) is increasingly utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). Patients with cancer have high information needs and the Internet has materialized as a leading source of information for many patients. Nevertheless, little is known about the availability, accessibility, quality, and readability of online information regarding NT for PDAC.

A search of online patient informational materials (PIMs) pertaining to NT for PDAC was conducted using a combination of common search engines and browsers. Two independent researchers evaluated the readability, quality, and availability of unique PIMs from the top 25 websites from each search using validated measures.

Among the 130 websites retrieved, 46 (35.4%) unique PIMs focused on treatment of PDAC. Only 30 (23%) mentioned NT as a possible treatment option. Downstaging was the rationale for NT mentioned in the majority (90%) of websites. The mean quality and reliability of the 30 PIMs, assessed using the DISCERN instrument, was 3.3 ± 0.7, suggesting moderate quality/reliability. The mean readability score, assessed using the SMOG Grade tool, was 10.96 ± 1.49, which is equivalent to an 11th grade reading level.

The low availability, poor readability, and moderate quality of online informational materials regarding NT for PDAC highlight the need for new patient-centered resources to educate patients and caregivers on an increasingly utilized treatment strategy for localized PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease process with a 5-year survival rate of only 11%. Neoadjuvant therapy in patients with localized pancreatic cancer has multiple theoretical benefits, including improved patient selection for surgery, early delivery of systemic therapy, and assessment of response to therapy. Herein, we review key surgical considerations when selecting patients for neoadjuvant therapy and curative-intent resection. Accurate determination of resectability at diagnosis is critical and should be based on not only anatomic criteria but also biologic and clinical criteria to determine optimal treatment sequencing. Borderline resectable or locally advanced pancreatic cancer is best treated with neoadjuvant therapy and resection, including vascular resection and reconstruction when appropriate. Lastly, providing nutritional, prehabilitation, and supportive care interventions to improve patient fitness prior to surgical intervention and adequately address the adverse effects of therapy is critical.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease due to its late presentation and tendency to recur early even after optimal surgical resection. Currently, there are limited options for effective systemic therapy. In addition, PDAC typically generates an immune-suppressive tumor microenvironment; trials of immunotherapy in metastatic PDAC have yielded disappointing results. There is considerable interest in using immunotherapy approaches in the neoadjuvant setting in order to prime the immune system to detect and prevent micrometastatic disease and recurrence. A scoping review was conducted to identify published and ongoing trials utilizing preoperative immunotherapy. In total, 9 published trials and 27 ongoing trials were identified. The published trials included neoadjuvant immune checkpoint inhibitors, cancer vaccines, and other immune-modulating agents that target mechanisms distinct from that of immune checkpoint inhibition. Most of these are early phase trials which suggest improvements in disease-free and overall survival when combined with standard neoadjuvant therapy. Ongoing trials are exploring various combinations of these agents with each other and with chemotherapy and/or radiation. Rational combination immunotherapy in addition to standard neoadjuvant therapy has the potential to improve outcomes in PDAC, but further clinical trials are needed, particularly those which utilize an adaptive trial design.

For logistical reasons, some high-volume centers have developed surgical programs wherein 1 surgical team performs 2 pancreatoduodenectomies on a single day. It is unclear whether this practice has a negative impact on surgical outcome.

We conuducted a retrospective analysis including all consecutive open pancreatoduodenectomies in a single high-volume center (2014-2021). Pancreatoduodenectomies were grouped as the first (pancreatoduodenectomy-1) or second (pancreatoduodenectomy-2) pancreatoduodenectomy on a single day (ie, paired pancreatoduodenectomies) and as pancreatoduodenectomy-3 whenever 1 pancreatoduodenectomy was performed per day (ie, unpaired). Patients undergoing minimally invasive procedures were excluded. The primary outcomes were major morbidity (ie, Clavien-Dindo grade ≥IIIa) and mortality.

Among 689 patients, 151 patients had undergone minimally invasive pancreatoduodenectomy, leaving 538 patients after open pancreatoduodenectomy for inclusion. The overall rate of major morbidity was 37.4% (n = 200/538) and in-hospital/30-day mortality 1.7% (n = 9/538). Overall, 136 (25.3%) patients were operated in 68 pancreatoduodenectomy-1/ pancreatoduodenectomy-2 pairs and 402 (74.7%) patients as unpaired pancreatoduodenectomy (pancreatoduodenectomy-3). No differences were found between pancreatoduodenectomy-1 and pancreatoduodenectomy-2 regarding the rates of major morbidity (35.3% vs 26.5%; P = .265) and mortality (1.5% vs 0%; P = .999). Between the 68 pancreatoduodenectomy-1/ pancreatoduodenectomy-2 pairs and the 402 unpaired pancreatoduodenectomies, the rates of major morbidity (30.9% vs 39.6%; P = .071) and mortality (0.7% vs 2.0%; P = .461) did not differ significantly. In multivariable logistic regression analysis, pancreatoduodenectomy-1 was not associated with major morbidity (odds ratio = 0.913 [95% confidence interval 0.515-1.620]; P = .756), whereas pancreatoduodenectomy-2 was associated with less major morbidity (odds ratio = 0.522 [95% confidence interval 0.277-0.983]; P = .045).

In a high-volume setting, performing 2 consecutive open pancreatoduodenectomies on a single operating day appears to be safe. This approach may be an option when logistically required.

Neoadjuvant therapy is increasingly being used before surgery for localized pancreatic cancer. Given the importance of completing multimodal therapy, the aim of this study was to characterize surgical resection rates after neoadjuvant therapy as well as the reasons for, and long-term prognostic impact of, not undergoing resection.

A systematic review and meta-analysis of prospective trials and high-quality retrospective studies since 2010 was performed to calculate pooled resection rates using a generalized random-effects model for potentially resectable, borderline resectable, and locally advanced pancreatic cancer. Median survival times were calculated using random-effects models for patients who did and did not undergo resection.

In 125 studies that met the inclusion criteria, neoadjuvant therapy consisted of chemotherapy (36.8 per cent), chemoradiation (15.2 per cent), or chemotherapy and radiation (48.0 per cent). Among 11 713 patients, the pooled resection rates were 77.4 (95 per cent c.i. 71.3 to 82.5), 60.6 (54.8 to 66.1), and 22.2 (16.7 to 29.0) per cent for potentially resectable, borderline resectable, and locally advanced pancreatic cancer respectively. The most common reasons for not undergoing resection were distant progression for resectable and borderline resectable cancers, and local unresectability for locally advanced disease. Among 42 studies with survival data available, achieving surgical resection after neoadjuvant therapy was associated with improved survival for patients with potentially resectable (median 38.5 versus 13.3 months), borderline resectable (32.3 versus 13.9 months), and locally advanced (30.0 versus 14.6 months) pancreatic cancer (P < 0.001 for all).

Although rates of surgical resection after neoadjuvant therapy vary based on anatomical stage, surgery is associated with improved survival for all patients with localized pancreatic cancer. These pooled resection and survival rates may inform patient-provider decision-making and serve as important benchmarks for future prospective trials.

Pancreatic ductal adenocarcinoma is an aggressive malignancy that carries a poor prognosis because the majority of patients present with locally advanced or metastatic disease. However, even patients who are fortunate enough to present with resectable disease are often plagued by high recurrence rates. While adjuvant chemotherapy has been shown to decrease the risk of recurrence after surgery, post operative complications and poor performance status after surgery prevent up to 50% of patients from receiving it. Given the benefits of neoadjuvant therapy in patients with borderline resectable disease, it is understandable that neoadjuvant therapy has been steadily increasing in patients with resectable cancers as well. In this review paper, we highlight the rational and existing evidence of using neoadjuvant therapy in all patients with resectable pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a poor prognosis. PDAC has poor response to immunotherapy because of its unique tumour microenvironment (TME). In an attempt to stimulate immunologically silent pancreatic cancer, we investigated the role of epigenetic therapy in modulating the TME to improve immunogenicity.

In vitro human PDAC cell lines MiaPaca2 and S2-013 were treated with 5μ m 3-Deazaneplanocin A (DZNep, an EZH2 inhibitor) and 5 μ m 5-Azacytidine (5-AZA, a DNMT1 inhibitor). In vivo orthotopic murine tumour models using both murine PAN02 cells and KPC cells inoculated in immunocompetent C56/BL7 mice were treated with anti-PD-L1 combined with DZNep and 5-AZA. Short hairpin knockdown (KD) of EZH2 and DNMT1 in PAN02 cells for the orthotopic murine tumour model was established to validate the drug treatment (DZNep and 5-AZA). qRT-PCR and microarray assays were performed for the evaluation of Th1-attracting chemokines and cancer-associated antigen induction.

Drug treatments induced significant upregulation of gene expressions of Th1-attracting chemokines, CXCL9 and CXCL10, and the cancer-testis antigens, NY-ESO-1, LAGE and SSX-4 (P < 0.05). In orthotopic tumour models, inoculation of PAN02 cells or KPC cells demonstrated significant tumour regression with corresponding increased apoptosis and infiltration of cytotoxic T lymphocytes in the combination treatment group. In the orthotopic Pan02-KD model, the anti-PD-L1 treatment also caused significant tumour regression.

We demonstrate that immunotherapy for PDAC can be potentiated with epigenetic therapy by increasing cancer-associated antigen expression and increased T-cell trafficking across the immunosuppressive tumour microenvironment via upregulation of the repressed chemokines and increased apoptosis with subsequent tumour regression.

The seventh leading cause of cancer-related death globally, pancreatic ductal adenocarcinoma (PDAC) involves the exocrine pancreas and constitutes greater than 90% of all pancreatic cancers. Surgical resection in combination with systemic chemotherapy with or without radiation remains the mainstay of treatment and the only potentially curative treatment option. While there has been improvement in systemic chemotherapy, long-term survival among patients with PDAC remains poor. Improvement in the understanding of tumorigenesis, genetic mutations, the tumor microenvironment (TME), immunotherapies, as well as targeted therapies continued to drive advances in PDAC treatment. We herein review the TME, genetic landscape, as well as various metabolic pathways associated with PDAC tumorigenesis relative to emerging therapies.

Physicians are increasingly recommending neoadjuvant therapy (NT) before surgery for pancreatic ductal adenocarcinoma (PDAC). However, patient preferences for and opinions regarding NT are poorly understood.

Survivors and caregivers from a national PDAC patient advocacy organization completed an online survey assessing preferences for NT versus surgery first (SF) and factors influencing their decision making.

Among 54 participants, 74.1% had a personal history of PDAC. While most patients preferred SF for resectable disease, NT was the preferred treatment approach for borderline resectable, locally advanced, and resectable cancers with high carbohydrate antigen 19-9. The most important factor influencing patient decision making regarding NT was its impact on overall survival while the least important was published national guidelines. The most preferred rationale for NT was ability to downstage to surgical resection and early treatment of micrometastatic disease.

Among a national cohort of PDAC survivors and caregivers, the majority preferred SF for resectable PDAC, whereas NT was preferred when the resectability of a tumor was in question. The impact of NT on quantity and quality of life, as well as the likelihood of achieving surgical resection, was most highly valued by participants.

Neoadjuvant therapy (NT) has increasingly been utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). It is the recommended approach for borderline resectable (BR) and locally advanced (LA) cancers and an increasingly utilized option for potentially resectable (PR) disease. Despite its increased use, little research has focused on patient-centered metrics among patients undergoing NT, including patient experiences, preferences, and recommendations. A better understanding of all aspects of the patient experience during NT may identify opportunities to design interventions aimed at improving quality of life; it may also facilitate the completion of NT and receipt of surgery, ultimately optimizing long-term outcomes.

To understand the experience of patients initiating and receiving NT to identify opportunities to improve neoadjuvant cancer care delivery.

Semi-structured interviews of patients with localized PDAC during NT were conducted to explore their experience initiating and receiving NT. Interviews took place between August 2020 and October 2021. Due to the descriptive nature of the research, questions were open ended. Interviews were conducted over the phone, audio recorded and then transcribed. All interviews were coded by two independent researchers using NVivo 12, iteratively identifying themes until thematic saturation was achieved. An integrative approach to qualitative analysis was used, utilizing both inductive and deductive methods.

A total of 12 patients with localized PDAC were interviewed. Patients with BR (n = 7), PR (n = 2), and LA (n = 3) cancers participated in the study. All patients indicated that choosing NT was the doctor's recommendation, while most reported not being familiar with the concept of NT (n = 11) and that NT was presented as the only option (n = 8). Five themes describing the patient experience emerged: physical symptoms, emotional symptoms, coping mechanisms, access to care, and life factors. The most commonly cited recommendation for improving the experience of NT was improved education before and during NT (n = 7). Patients highlighted the need for more information on the rationale behind choosing NT prior to surgery, the anticipated surgery and its likelihood of surgery occurring after NT, as well as general information prior to starting NT treatment. The need for seeing different members of the healthcare team, including ancillary services was also frequently cited as a recommendation for improving the experience of NT (n = 5).

This study provides a framework to allow for a better understanding of the PDAC patient experience during NT and highlights opportunities to improve quality and quantity of life outcomes.

Neoadjuvant therapy (NT) is increasingly utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). Given the importance of completing multimodality therapy, the purpose of this qualitative study was to characterize physician perspectives on barriers and facilitators to delivering NT.

A purposive sample of surgical, medical, and radiation oncologists participated in semi-structured interviews. Interviews were transcribed and coded by 3 independent researchers, iteratively identifying themes until saturation was achieved.

Participants (n = 27) were heterogeneous in specialty, years of experience, practice setting, gender, and geography. The most commonly cited advantage of NT was the ability to downstage patients. The most commonly cited barriers included lack of access and limited evidence. Patient preference for immediate surgery was frequently cited as a barrier, but most participants felt that patients eventually understood the treatment recommendation after informed discussion. Recommendations to enhance the delivery of NT included improved patient education, communication, and better evidence.

In this qualitative study, indications for, barriers to, and opportunities to improve the delivery of NT for localized PDAC were identified. These results highlight the need for better evidence and protocol standardization for NT as well as methods of improving care coordination, communication, and education to improve patient-centered outcomes.

Worldwide, there is a shifting paradigm from immediate surgery with adjuvant treatment to a neoadjuvant approach for patients with resectable or borderline resectable pancreatic cancer (RPC or BRPC). Comparison of neoadjuvant and adjuvant studies is extremely difficult because of a great difference in patient selection. The evidence from randomized studies shows that overall survival by intention-to-treat improves after neoadjuvant gemcitabine-based chemoradiotherapy or chemotherapy (various regimens), as compared to immediate surgery followed by adjuvant chemotherapy. Radiotherapy appears to play an important role in mediating locoregional effects. Yet, since more effective chemotherapy regimens are currently available, in particular FOLFIRINOX and Gemcitabine/Nab-paclitaxel, these chemotherapy regimens should be investigated in future randomized trials combined with (stereotactic) radiotherapy to further improve outcomes of RPC and BRPC.

Neoadjuvant therapy (NT) is increasingly used for localized pancreatic ductal adenocarcinoma (PDAC). The impact of care fragmentation during NT on the outcomes of patients with PDAC is unknown.

Adult patients with Stage I-III PDAC who received NT and patients who underwent surgery first followed by adjuvant therapy (AT) between 2004 and 2016 were queried from the National Cancer Database. Short- and long-term outcomes were compared between patients who received fragmented care (FC; care provided at >1 hospital) versus integrated care (IC; care at a single institution).

Among 6522 patients who underwent NT before pancreatectomy, 3755 (57.6%) received FC and 2767 (42.4%) received IC. While patients who received FC had a longer time to initiation of treatment (33.2 vs. 29.7 days, p < 0.001), there was no difference in median overall survival (OS) (26.7 vs. 26.5 months, p = 0.6). Among patients who underwent upfront surgery followed by AT (n = 15 291), patients who received FC had a longer time from diagnosis to undergoing surgery but less time from surgery to AT and no difference in OS (24.0 vs. 24.0 months, p = 0.910).

Although care fragmentation was associated with slightly longer times to initiate and complete treatment among patients with localized PDAC, long-term survival outcomes were similar.

Despite recent advances in the multimodal treatment of pancreatic ductal adenocarcinoma (PDAC), overall survival remains poor with a 5-year cumulative survival of approximately 10%. Neoadjuvant (chemo- and/or radio-) therapy is increasingly incorporated in treatment strategies for patients with (borderline) resectable and locally advanced disease. Neoadjuvant therapy aims to improve radical resection rates by reducing tumor mass and (partial) encasement of important vascular structures, as well as eradicating occult micrometastases. Results from recent multicenter clinical trials evaluating this approach demonstrate prolonged survival and increased complete surgical resection rates (R0). Currently, tumor response to neoadjuvant therapy is monitored using computed tomography (CT) following the RECIST 1.1 criteria. Accurate assessment of neoadjuvant treatment response and tumor resectability is considered a major challenge, as current conventional imaging modalities provide limited accuracy and specificity for discrimination between necrosis, fibrosis, and remaining vital tumor tissue. As a consequence, resections with tumor-positive margins and subsequent early locoregional tumor recurrences are observed in a substantial number of patients following surgical resection with curative intent. Of these patients, up to 80% are diagnosed with recurrent disease after a median disease-free interval of merely 8 months. These numbers underline the urgent need to improve imaging modalities for more accurate assessment of therapy response and subsequent re-staging of disease, thereby aiming to optimize individual patient's treatment strategy. In cases of curative intent resection, additional intra-operative real-time guidance could aid surgeons during complex procedures and potentially reduce the rate of incomplete resections and early (locoregional) tumor recurrences. In recent years intraoperative imaging in cancer has made a shift towards tumor-specific molecular targeting. Several important molecular targets have been identified that show overexpression in PDAC, for example: CA19.9, CEA, EGFR, VEGFR/VEGF-A, uPA/uPAR, and various integrins. Tumor-targeted PET/CT combined with intraoperative fluorescence imaging, could provide valuable information for tumor detection and staging, therapy response evaluation with re-staging of disease and intraoperative guidance during surgical resection of PDAC.

A literature search in the PubMed database and (inter)national trial registers was conducted, focusing on studies published over the last 15 years. Data and information of eligible articles regarding PET/CT as well as fluorescence imaging in PDAC were reviewed. Areas covered: This review covers the current strategies, obstacles, challenges, and developments in targeted tumor imaging, focusing on the feasibility and value of PET/CT and fluorescence imaging for integration in the work-up and treatment of PDAC. An overview is given of identified targets and their characteristics, as well as the available literature of conducted and ongoing clinical and preclinical trials evaluating PDAC-targeted nuclear and fluorescent tracers.