Staging Of Pancreatic Cancer Research Articles

An update on pancreatic cancer imaging, staging and use of the PACT-UK radiology template pre- and post-neoadjuvant treatment.

Pancreatic ductal adenocarcinoma continues to have a poor prognosis, although recent advances in neoadjuvant treatments have provided some hope. Imaging assessment of suspected tumours can be challenging and requires a specific approach, with pancreas protocol CT being the primary imaging modality for staging with other modalities used as problem-solving tools to facilitate appropriate management. Imaging assessment post neoadjuvant treatment can be particularly difficult due to a current lack of robust radiological criteria to predict response and differentiate treatment induced fibrosis/inflammation from residual tumour. This review aims to provide an update of pancreatic ductal adenocarcinoma with particular focus on three points: tumour staging pre- and post-neoadjuvant treatment including vascular assessment, structured reporting with introduction of the PACT-UK radiology template (PAncreatic Cancer reporting Template-UK), and the potential future role of artificial intelligence in the diagnosis and staging of pancreatic cancer.

Quantitative detection of miR-25 for early diagnosis, postoperative assessment and TNM staging of pancreatic cancer

Objectives: Pancreatic cancer is one of the most common malignant tumors of the digestive tract. Due to its strong concealment and rapid disease progress, it is characterized by high mortality and low cure rate. Current research focuses on screening high-risk populations, preventing the occurrence of pancreatic cancer and developing imaging technology and tumor markers for early diagnosis. This study aimed to investigate the absolute quantitative detection of microRNA-25 (miR-25) and reveal its quantitative changes in the treatment of pancreatic cancer. We compared serum miR-25 level between pancreatic cancer patients and other tumor patients, especially those with gastrointestinal cancer, to provide further evidence for early diagnosis, differential diagnosis and prognosis of pancreatic cancer. Methods: We collected serum samples from 51 pancreatic cancer patients (including 21 patients with preoperative and postoperative samples), 52 pancreatitis patients, 141 other tumor patients, and 50 healthy individuals from Huashan Hospital, Fudan University. The serum levels of miR-25, Carbohydrate Antigen 19–9 (CA19–9), Carbohydrate Antigen 125 (CA125) and Carcinoembryonic Antigen (CEA) in these populations were measured to analyze the value of miR-25 quantitative detection in the diagnosis, postoperative assessment and Tumor Node Metastasis (TNM) staging of pancreatic cancer. Results: Among the 51 pancreatic cancer patients, 50 cases (98.04 %) showed miR-25 levels above the threshold (3333 copies/μl), while all samples in normal group showed negative. The mean level of miR-25 in serum was 5707.45 ± 361.02 copies/μl. In other tumor groups, 21/141 (14.89 %) patients showed positive results and the mean miR-25 level was 847.09 ± 125.97 copies/μl. Comparing before and after operation in 21 paired samples, the level of miR-25 declined significantly after operation, with an average decline rate of 86.36 %. Conclusions: Serum miR-25 levels were significantly higher in pancreatic cancer patients compared to both normal and other tumor groups and decreased significantly after surgery. In addition, miR-25 showed higher sensitivity than common tumor markers (CA19–9, CA125, CEA) in early diagnosis of pancreatic cancer, and proved to be of significant value in evaluating the effect of surgical treatment.

Investigation of Programmed Death Ligand-1 as a New Prognostic Biomarker in Pancreatic Cancer Patients.

Pancreatic cancer is one of the most lethal and fast-growing cancers with a poor prognosis. Herein, we report the expression of programmed death ligand 1 (PD-L1) as a new prognostic biomarker in pancreatic cancer progression analysis at the clinical level. Immunohistochemistry was performed on 86 clinically proven cases of pancreatic cancer tissue microarrays (TMAs) using anti-PD-L1 antibodies. Histoscore was done, and a variety of cutoffs were identified for analyses of the results. The chi-square test and Kaplan-Meier method were used to find the association between pancreatic cancer and various clinicopathological variables and the overall survival of the patients. PD-L1 expression was associated with histological grade and recurrence of the disease for epithelial and stromal staining at 10 histoscores. In addition, PD-L1 expression was strongly associated with lymph node involvement at the stromal 20 histoscore. The tumor stage of pancreatic cancer had an association with PD-L1 expression with epithelial and stromal 20 histoscores for all comparisons. At a stromal 20 histoscore, overall survival in high-low expression of PD-L1 was 7-19 months, and at a nuclear/cytoplasmic 10 histoscore, it was 9-28 months (p = 0.0001), respectively. Overall, PD-L1 overexpression in subcellular compartments was associated with disease aggression phenotypes and poor patient survival. Overexpression of PD-L1 was directly linked to pancreatic cancer progression and a poor survival rate. Therefore, PD-L1 may be used as a prognostic biomarker in the diagnosis, treatment, and management of pancreatic cancer patients.

Uptake of germline genetic testing in patients with advanced breast, ovarian, pancreatic, or prostate cancer.

19 Background: With FDA approval of PARP inhibitors for treatment of BRCA1/2 -associated advanced breast, ovarian, pancreatic, and prostate cancer, National Comprehensive Cancer Network guidelines for germline genetic testing (GGT) have expanded for patients with these tumor types since 2019. We aimed to analyze factors associated with GGT uptake in these patient populations. Methods: We conducted a retrospective cohort study among patients diagnosed with metastatic breast and prostate cancer and all stages of ovarian and pancreatic cancer in 2020-2023 at Columbia University Irving Medical Center in New York City. We extracted data from the electronic medical record on demographics (age at diagnosis, sex, race/ethnicity, Jewish ancestry, marital status) and clinical characteristics (tumor type, year of diagnosis, family history of cancer, receipt of somatic testing, genetic counseling, targeted therapy). The primary outcome was receipt of GGT. Descriptive statistics were generated and multivariable logistic regression analyses were used to estimate the association between demographic/clinical factors and GGT uptake. Results: Among 884 evaluable patients, mean age was 67 years (SD, 14) and the study population included 45% Whites, 15% Blacks, 21% Hispanics, and 9% Asians/Others; 14% had Jewish ancestry. Only 16% were seen by a genetic counselor, 66% had undergone GGT, and 57% had somatic testing. After adjustment for confounders, younger age, Jewish ancestry, later year at diagnosis, and family history of breast or pancreatic cancer were significantly associated with GGT uptake. Patients with pancreatic or prostate cancer were about 60% less likely to undergo GGT compared to patients with ovarian cancer. Patients who had somatic testing were over 4.5-fold more likely to receive GGT. No significant differences were observed based upon sex or race/ethnicity. Among patients who underwent GGT, 20% were found to have a PV and over half of patients who received targeted therapy had PVs detected. Conclusions: We observed increasing use of oncologist-led GGT over time with over 65% of patients with advanced breast, ovarian, pancreatic, or prostate cancer undergoing testing, of which 20% had PVs detected. Given the evolution of targeted therapies and the potential downstream impact of known PVs for family members, under-utilization of GGT in patients with pancreatic and prostate cancer as well as older individuals should be addressed in future studies.

Synergistic effects of calcium channel blockers and renin-angiotensin inhibitors with gemcitabine-based chemotherapy on the survival of patients with pancreatic cancer

PurposePancreatic cancer remains a significant public health challenge, with poor long-term outcomes due to the lack of effective treatment options. Repurposing commonly used clinical drugs, such as ACE inhibitors, ARBs, CCBs, and metformin, may enhance the efficacy of chemotherapy and offer a promising therapeutic strategy for improving patient outcomes.MethodsA retrospective analysis of concomitant treatment with ACE-Is, ARBs, CCBs, and metformin alongside gemcitabine chemotherapy in patients with pancreatic cancer was conducted. Treatment responses were evaluated, with overall survival (OS) estimated using the Kaplan–Meier method. Additionally, the Cox proportional hazards model was employed to assess the impact of these specific agents on patient survival.Results4628 patients with various stages of pancreatic cancer were identified in the database between 2007 and 2016. The estimated overall survival (OS) in the analyzed group was 6.9 months (95% CI 6.4–7). The use of any of the analyzed drugs was associated with a significant improvement in mOS of 7.5 months (95% CI 6.8–7.8) vs. 6.7 months (95% CI 6.4–7.0) for patients who did not have additional treatment (p < 0.0001). ARBs, ACE-Is, CCBs, and metformin varied in their effectiveness in prolonging mOS among patients. The longest mOS of 8.9 months (95% CI 7.7–11.6) was observed in patients receiving additional therapy with ARBs, while the shortest mOS of 7.7 months (95% CI 6.5–8.9) was achieved by patients receiving metformin. In the adjusted Cox analysis, metformin was associated with a significantly weaker effect on mOS (p = 0.029). A particularly interesting trend in prolonging 5-year survival was demonstrated by ARBs and CCBs with 14.1% (95% CI 9–22%) and 14.8% (95% CI 11.1–19.6%), respectively, compared to patients not taking these drugs, who achieved a 5-year OS of 3.8% (95% CI 3.2–4.4%).ConclusionOur results demonstrate a significant positive impact of ARBs, ACE inhibitors, and CCBs on survival in patients with pancreatic cancer treated with gemcitabine. The addition of these inexpensive and relatively safe drugs in patients with additional comorbidities may represent a potential therapeutic option in this indication. However, prospective clinical trials to evaluate the optimal patient population and further studies to determine the potential impact of these agents on chemotherapy are necessary.

Accelerated Exosomal Metabolic Profiling Enabled by Robust On-Target Array Sintering with Metal-Organic Frameworks.

Pancreatic cancer is highly lethal, and survival chances improve only with early detection at a precancerous stage. However, there remains a significant gap in developing tools for large-scale, rapid screening. To this end, a high-throughput On-Target Array Extraction Platform (OTAEP) by direct sintering of a series of metal-organic frameworks (MOFs) for dual in situ extraction, encompassing both exosomes and their metabolic profiles, is developed. Based on the principle of geometry-dependent photothermal conversion efficiency and standard testing, the appropriate MOF functional unit is identified. This unit enables exosome enrichment within 10 min and metabolic fingerprint extraction in under 1 s of laser irradiation, with over five reuse. To further accelerate and enhance the quality of metabolic profile analysis, the application of Surrogate Variable Analysis to eliminate hidden confounding factors within the profiles is proposed, and five biomarkers demonstrated by MS/MS experiments are identified. These biomarkers enable early diagnosis, risk stratification, and staging of pancreatic cancer simultaneously, with sensitivity of 94.1%, specificity of 98.8%, and precision of 94.9%. This work represents a breakthrough for overcoming throughput challenges in large-scale testing and for addressing confounding factors in big data analysis.

Advancements in Early Detection and Screening Strategies for Pancreatic Cancer: From Genetic Susceptibility to Novel Biomarkers.

Pancreatic cancer is a rare but lethal cancer due to its biologically aggressive nature, advanced stage at the time of diagnosis, and poor response to oncologic therapies. The risk of pancreatic cancer is significantly higher to 5% in certain high-risk individuals with inherited genetic susceptibility. Screening for pancreatic cancer in these individuals from high-risk groups can help with the early detection of pancreatic cancer as well as the detection of precursor lesions leading to early surgical resection and improved overall outcomes. The advancements in radiological imaging as well as advanced endoscopic procedures has made a significant impact on the early diagnosis, surveillance, and staging of pancreatic cancer. There is also a significant advancement in the development of biomarkers for the early detection of pancreatic cancer, which has also led to the development of liquid biopsy, allowing for microRNA detection in serum and circulating tumor cells. Various societies and organizations have provided guidelines for pancreatic cancer screening and surveillance in high-risk individuals. In this review, we aim to discuss the hereditary risk factors for developing pancreatic cancer, summarize the screening recommendations by different societies, and discuss the development of novel biomarkers and areas for future research in pancreatic cancer screening for high-risk individuals.

Highly sensitive microfluidic sensor using integrated optical fiber and real-time single-cell Raman spectroscopy for diagnosis of pancreatic cancer

Pancreatic cancer is notoriously lethal due to its late diagnosis and poor patient response to treatments, posing a significant clinical challenge. This study introduced a novel approach that combines a single-cell capturing platform, tumor-targeted silver (Ag) nanoprobes, and precisely docking tapered fiber integrated with Raman spectroscopy. This approach focuses on early detection and progression monitoring of pancreatic cancer. Utilizing tumor-targeted Ag nanoparticles and tapered multimode fibers enhances Raman signals, minimizes light loss, and reduces background noise. This advanced Raman system allows for detailed molecular spectroscopic examination of individual cells, offering more practical information and enabling earlier detection and accurate staging of pancreatic cancer compared to conventional multicellular Raman spectroscopy. Transcriptomic analysis using high-throughput gene screening and transcriptomic databases confirmed the ability and accuracy of this method to identify molecular changes in normal, early, and metastatic pancreatic cancer cells. Key findings revealed that cell adhesion, migration, and the extracellular matrix are closely related to single-cell Raman spectroscopy (SCRS) results, highlighting components such as collagen, phospholipids, and carotene. Therefore, the SCRS approach provides a comprehensive view of the molecular composition, biological function, and material changes in cells, offering a novel, accurate, reliable, rapid, and efficient method for diagnosing and monitoring pancreatic cancer.

Treatment and Prognosis for Pancreatic Duct Disruption Associated With Pancreatic Cancer: A Case Series of 15 Patients.

Background Pancreatic duct (PD) disruption can occasionally be attributed to pancreatic cancer. Therapeutic interventions for PD disruption due to pancreatic cancer and their influence on pancreatic cancer prognosis remain unclear. This study investigated the therapeutic modalities and prognostic implications of PD disruption in pancreatic cancer. Methods This retrospective study included 15 patients with PD disruption concomitant with pancreatic cancer between April 2011 and March 2023. As an endoscopic intervention for PD disruption, endoscopic pancreatic stenting (EPS) or endoscopic ultrasonography-guided pancreatic fluid collection drainage (EUS-PFD) was performed. Technical success was defined as stent placement and clinical success was defined as an improvement in PD disruption. Results Of the 15 cases of PD disruption, two involved only pancreatic juice leakage without symptoms, four involved pancreatic pseudocyst (PPC) without infection, and nine involved PPC with infection. Four patients underwent EPS, nine underwent EUS-PFD, and two underwent lumen-apposing metal stent placement. All patients achieved both technical and clinical success without complications. The clinical stage of pancreatic cancer ranged from carcinoma in situ to the metastatic phase. For the treatment of pancreatic cancer, five patients underwent surgical resection, and eight underwent chemotherapy. There was no obvious recurrence of peritoneal sowing. The median overall survival from the diagnosis of pancreatic cancer in the resected and non-resected cases was 74 and 9.6 months, respectively. Conclusion Endoscopic intervention was effective in all cases of PD disruption due to pancreatic cancer. Furthermore, even in cases of pancreatic cancer after PD disruption, survival rates were similar to those in cases without PD disruption and were achieved through surgical resection or chemotherapy.

The EFNA4 gene is a potential prognostic biomarker in pancreatic cancer: a bioinformatics analysis.

Pancreatic cancer is a highly aggressive malignancy with poor prognosis, and there is an urgent need to understand its molecular mechanisms for early diagnosis and treatment. Despite surgical resection being the only effective treatment, most patients are diagnosed at an advanced stage, missing the optimal window for therapy. Identifying novel biomarkers is crucial for prognostic assessment, treatment planning, and early intervention. Ephrin A4 (EFNA4), a member of the receptor tyrosine kinase family, is involved in vascular and epithelial development via regulation of cell migration and rejection. However, the role of EFNA4 in pancreatic cancer has not been reported. Therefore, our study aimed to clarify the role of EFNA4 in pancreatic cancer through bioinformatics analysis and vitro experiments. The expression of EFNA4 and its potential value as a diagnostic and prognostic biomarker in pancreatic cancer was analyzed using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) database. According to the expression level of EFNA4, patients were divided into high expression group and low expression group, and the correlation between overall survival (OS) and disease-free survival (DFS) with different expression levels of EFNA4 and clinical parameters were analyzed. Subsequently, reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect EFNA4 expression. The proliferation, invasion, and cloning ability of the cells were detected via Cell Counting Kit 8 (CCK8), Transwell, and plate cloning assays, respectively. EFNA4 is highly expressed in pancreatic cancer, and upregulation of EFNA4 is associated with poor prognosis. In this study, EFNA4 expression was correlated with T stage and TNM (tumor-node-metastasis) stage of pancreatic cancer, and the median survival time and progression-free survival (PFS) were worse in those with high EFNA4 expression (394 days) than in those with low expression (525 days) [hazard ratio (HR): 1.47, 95% confidence interval (CI): 1.00-2.16, P=0.047]. In addition, EFNA4 was also found to be involved in the regulation of signal pathways such as cell adhesion, cyclic AMP, insulin secretion, pancreatic secretion, and protein digestion and absorption. In vitro experiments demonstrated that EFNA4 knockdown significantly inhibited the proliferation, cloning ability, and invasiveness of the PANC-1 and SW1990 pancreatic cancer cell lines. The abnormal expression of EFNA4 in pancreatic cancer is associated with poor prognosis. Knockout of EFNA4 gene could significantly inhibit the proliferation and invasion of pancreatic cancer cells. Therefore, EFNA4 may be one of the molecular targets for poor prognosis of patients with pancreatic cancer.

Drug delivery particles for targeted imaging-guided photothermal/chemotherapy synergy cancer therapy

The early stage of pancreatic cancer is asymptomatic and the treatment effect is not ideal. The progression to the advanced stage leads to a close relationship between mortality and morbidity. Therefore, there is an urgent need to develop precise and efficient therapeutic strategies to combat pancreatic cancer. In this study, we introduce a near-infrared (NIR) targeted drug delivery nanoparticle for ultrasound (US) imaging to guide magnetothermal/chemotherapy synergistic treatment of pancreatic cancer. Carboxylated polylactic acid (PLGA-PEG-COOH) serves as the structure of the nanoparticles, specifically binding the RGD cyclic peptide for pancreatic cancer targeting activity and promoting tumor aggregation of the nanoparticles. NIR-induced superparamagnetic iron oxide (SPIO) nanoparticles convert near-infrared light into thermal energy, triggering vaporization of perfluoropentane (PFH) droplets to generate PFH bubbles that enhance US imaging and help load doxorubicin (DOX), which are released from nanoparticles. SPIO can also be used for thermal ablation of tumors to improve therapeutic effect in treating pancreatic cancer. The results show that the targeted particles mediated by NIR have the characteristics of targeted drug delivery imaging. The microspheres exhibit strong acoustic and near-infrared responsiveness. Cell proliferation experiments showed that IR-mediated PFH-DOX@PLGA/SPIO-RGD NPs (RNPs) had a higher inhibitory effect on cell proliferation. Animal experiments have shown that RNPS can accumulate highly in the tumor area and show good therapeutic effect. In conclusion, this nanotherapeutic particle is a very promising targeted image-guided photothermal/chemotherapeutic synergistic tumor therapy strategy.

Early detection of pancreatic cancer

The diagnosis of pancreatic cancer associates an appalling significance. Detection of preinvasive stage of pancreatic cancer will ameliorate the survival of this deadly disease. Premalignant lesions such as Intraductal Papillary Mucinous Neoplasms or Mucinous Cystic Neoplasms of the pancreas are detectable on imaging exams and this permits their management prior their invasive development. Pancreatic intraepithelial neoplasms (PanIN) are the most frequent precursors of pancreatic adenocarcinoma (PDAC), and its particular type PanIN high-grade represents the malignant non-invasive form of PDAC. Unfortunately, PanINs are not detectable on radiologic exams. Nevertheless, they can associate indirect imaging signs which would rise the diagnostic suspicion. When this suspicion is established, the patient will be enrolled in a follow-up strategy that includes performing of blood test and serial imaging test such as computed tomography or magnetic resonance imaging, which will cost in the best-case scenario a burden of healthcare systems, and potential mortality in the worst-case scenario when the patient underwent resection surgery, worthless when there is no moderate or high grade dysplasia in the final histopathology. This issue will be avoid having at its disposal a diagnostic technique capable of detecting high-grade PanIN lesions, such is the cytology of pancreatic juice obtained by nasopancreatic intubation. Herein, we review the possibility of detection of early malignant lesions before they become invasive PADC.

The potential role of serial circulating tumor DNA (ctDNA) testing after upfront surgery to guide adjuvant chemotherapy for early stage pancreatic cancer: The AGITG DYNAMIC-Pancreas trial.

107 Background: Recurrence rates following upfront resection of pancreatic adenocarcinoma are high, with some benefit from adjuvant chemotherapy (AC). A biomarker that improves risk stratification and/or provides real time indication of AC benefit could improve routine clinical management and accelerate trial progress. Previous studies in pancreas cancer suggest that patients with detectable ctDNA post surgery are at an elevated risk of recurrence. Detectable ctDNA at the completion of AC may also be associated with an elevated recurrence risk. Methods: Patients with early stage pancreatic adenocarcinoma were enrolled following upfront resection at 26 Australian centres. Patients were ECOG 0-1 and fit for AC. A tumour-informed ctDNA assay was used to identify somatic mutations for tracking in circulating cell-free DNA. ctDNA+ patients received 6 months of AC (FOLFIRINOX or gemcitabine/capecitabine selected at the clinician's discretion), while ctDNA- patients could de-escalate to 3 months at the clinician’s discretion. ctDNA was assessed again at the end of AC. The primary study endpoint was the feasibility of ctDNA-guided therapy. Secondary endpoints included the association of ctDNA with clinicopathologic risk factors and survival outcomes. Results: A total of 102 patients were enrolled from March 2019 to Nov 2023. Median age was 68 years (range 41 – 86), with 50% male and 95% ECOG 0-1. Tumours were located in the head of pancreas in 72%. Histology revealed T1 (18%), T2 (50%), and T3 (32%) tumors, with nodal involvement in 71%, and an R0 resection in 77%. Post-operative Ca19-9 was elevated in 29%. Forty patients (40%) were ctDNA+ve post resection, 54 (53%) were ctDNA-ve, and no result was obtained in 4 (4%) due to the absence of tumor mutation, and as a result, they were considered ineligible. The presence or absence of ctDNA was not associated with known clinicopathologic risk factors. Median time to ctDNA collection was 5 weeks (range 3 – 9) and to commencing AC was 6 weeks (range 4-12). Of 54 ctDNA-ve patients, 24 (44%) were de-escalated to receive a planned 3 months of AC. With a median follow-up of 36 months (range 2-56) the median recurrence free survival (RFS) in ctDNA+ve patients was 13 months compared to 22 months for ctDNA-ve patients (HR 0.52, p = 0.003). Conclusions: A tumor informed ctDNA approach to AC selection is feasible for patients undergoing upfront resection of pancreatic adenocarcinoma, with the first blood draw to be scheduled at week 5, allowing time for ctDNA analysis to determine AC selection. A high proportion of patients had detectable ctDNA, which appears independent of known prognostic markers. ctDNA detection was associated with earlier recurrence. Analyses of the impact of changes in ctDNA over time on survival are ongoing. Clinical trial information: ACTN12618000335291.

The influence of modern computer and magnetic resonance imaging technologies on the preoperative staging of pancreatic cancer

Цель исследования: обзор и анализ зарубежной и отечественной литературы, клинических рекомендаций, посвященных оценке распространенности опухоли протоковой аденокарциномы поджелудочной железы и тактике лечения пациентов с выявленным новообразованием поджелудочной железы.Материал и методы. Проведен анализ отечественных и зарубежных источников литературы по базам PubMed с использованием ключевых слов “pancreatic cancer”, “vascular invasion”, “locally advanced cancer”, “cancer statistics”, “CT”, “MRI”, “neoadjuvant therapy” за последние 5–10 лет.В данном обзоре рассмотрены основные методы визуализации, используемые для определения взаимоотношения опухоли с прилежащими магистральными сосудами и оценки резектабельности рака поджелудочной железы.Заключение. Компьютерная томография и магнитно-резонансная томография с контрастным усилением – первоочередные методы диагностики протоковой аденокарциномы поджелудочной железы. Они высокоинформативны для оценки контакта/вовлечения сосудистых структур, распространенности опухолевого процесса, однако стандартные критерии неинформативны для оценки ответа на химиотерапевтическое лечение, поэтому требуется внедрение альтернативных способов его оценки, одним из которых является радиомика, лежащая в основе работы искусственного интеллекта и программ глубокого машинного обучения.

Implementation of Best Practices in Pancreatic Cancer Care in the Netherlands: A Stepped-Wedge Randomized Clinical Trial.

Implementation of new cancer treatment strategies as recommended by evidence-based guidelines is often slow and suboptimal. To improve the implementation of guideline-based best practices in the Netherlands in pancreatic cancer care and assess the impact on survival. This multicenter, stepped-wedge cluster randomized trial compared enhanced implementation of best practices with usual care in consecutive patients with all stages of pancreatic cancer. It took place from May 22, 2018 through July 9, 2020. Data were analyzed from April 1, 2022, through February 1, 2023. It included all patients in the Netherlands with pathologically or clinically diagnosed pancreatic ductal adenocarcinoma. This study reports 1-year follow-up (or shorter in case of deceased patients). The 5 best practices included optimal use of perioperative chemotherapy, palliative chemotherapy, pancreatic enzyme replacement therapy (PERT), referral to a dietician, and use of metal stents in patients with biliary obstruction. A 6-week implementation period was completed, in a randomized order, in all 17 Dutch networks for pancreatic cancer care. The primary outcome was 1-year survival. Secondary outcomes included adherence to best practices and quality of life (European Organisation for Research and Treatment of Cancer [EORTC] global health score). Overall, 5887 patients with pancreatic cancer (median age, 72.0 [IQR, 64.0-79.0] years; 50% female) were enrolled, 2641 before and 2939 after implementation of best practices (307 during wash-in period). One-year survival was 24% vs 23% (hazard ratio, 0.98, 95% CI, 0.88-1.08). There was no difference in the use of neoadjuvant chemotherapy (11% vs 11%), adjuvant chemotherapy (48% vs 51%), and referral to a dietician (59% vs 63%), while the use of palliative chemotherapy (24% vs 30%; odds ratio [OR], 1.38; 95% CI, 1.10-1.74), PERT (34% vs 45%; OR, 1.64; 95% CI, 1.28-2.11), and metal biliary stents increased (74% vs 83%; OR, 1.78; 95% CI, 1.13-2.80). The EORTC global health score did not improve (area under the curve, 43.9 vs 42.8; median difference, -1.09, 95% CI, -3.05 to 0.94). In this randomized clinical trial, implementation of 5 best practices in pancreatic cancer care did not improve 1-year survival and quality of life. The finding that most patients received no tumor-directed treatment paired with the poor survival highlights the need for more personalized treatment options. ClinicalTrials.gov Identifier: NCT03513705.

Management Modalities of Pancreatic Cancer and Surgical Outcomes of Braun's Anastomosis Addition in Whipple's Procedure: A Single-center Prospective Study

Background: Pancreatic cancer is an aggressive malignancy with high mortality rate. Many morbidities associated with Whipple's procedure that endanger patients’ life which need updated surgical techniques to lower these morbidities. The aim of this study is to determine management modalities of pancreatic cancer and surgical outcomes of adding Braun's jejunojejunostomy to Whipple's procedure for reduction of postoperative risks in Sudanese patients to reach excellent surgical practice. Subjects and Methods: This is a prospective-cohort study conducted during the period between January 2022 and July 2023 at Ibn Sina specialized hospital, Khartoum, Sudan, on sixty-three patients diagnosed with resectable pancreatic cancer. Addition of Braun’s jejunojejunostomy to elective open Whipple’s surgery was performed. Results: Seventy-three percent of patients diagnosed with pancreatic cancer were males with the ratio (3:1). Patients’ distribution according to age ranged between 46 and 60 years representing (41.3%). The significant reported comorbidities that associated with PC were diabetes mellitus (30.2%) and businessmen (39.7%). Most of patients were lived in rural areas (57.1%). Abdominopelvic CT-scan revealed stage (II) of pancreatic cancer in (68.2%) of patients. The predominant morbidity after addition of Braun's jejunojejunostomy was wound infections noticed in (17.5%) of patients. Moreover, other complications were categorized as follows: pulmonary infections in (6.35 %) of cases, postoperative diabetes mellitus in (4.76 %) of cases, entero-cutaneous fistula in (4.76 %) of cases, delayed gastric emptying in (3.17%) of cases, biliary leak in (3.17%) of cases, (3.17%) of cases, pancreatic fistula in one case (1.58%), gastric outlet obstruction in one case (1.58%) and postoperative GIT bleeding in one case (1.58%). Postoperative hospital stay of patients were ranged between 8-15 days for (66.7%) of cases. The mortality rate was zero. Conclusions: To reduce the rate of lethal surgical morbidities of Whipple's procedure, we recommend addition of Braun's jejunojejunostomy as useful technique. Moreover, it will potentially help in improving the quality of surgical practice and survival outcomes of patients who diagnosed with pancreatic cancer.

Abstract 2399: Stage-matched prognosis comparison between ypTNM and pTNM stage in pancreatic cancer

Abstract Introduction: The prognostic significance of pathological stage in pancreatic cancer is well-established. The 8th American Joint Commission on Cancer (AJCC) TNM staging introduced the ypTNM stage for neoadjuvant treatment (NAT) patients responding to the increased use of NAT. Despite this, there has been no comparative assessment of the prognosis between ypTNM and pTNM stages in pancreatic cancer. This study aimed to evaluate and compare the prognoses between ypTNM and pTNM stages in surgically resected pancreatic cancer. Method: A cohort of 586 patients who underwent pancreatic cancer surgery at a tertiary center from January 2018 to March 2022 was analyzed. Exclusions comprised those with prior pancreatectomy, suspicious liver metastasis or peritoneal seeding before NAT, those with open biopsy, R2 resection, and distant metastasis during operation, and postoperative mortalities or immediate follow-up losses. Clinicopathologic demographics underwent analysis, and a propensity score-matched (PSM) analysis (1:3) was conducted based on factors influencing overall survival (OS) in multivariate analysis. Subgroup analyses, categorized by stage, compared survival between ypTNM and pTNM stages. Results: The analysis included 541 patients, with 100 undergoing NAT (ypTNM) and 441 opting for upfront surgery (pTNM). Comparable OS was observed between ypTNM and pTNM patients (median 51.0 vs. 46.0 months, 3-year survival rate (YSR) 68.7% vs 56.3%, p = 0.094). Subgroup analysis by stages I (3YSR 76.8% vs 67.5%, p = 0.577), II (56.2% vs 53.0%, p = 0.715), and III (26.5% vs 28.7%, p = 0.596) revealed similar survival between ypTNM and pTNM. Multivariate analysis identified factors such as age &amp;gt;65 (HR 1.651, p = 0.002), CA19-9 &amp;gt;150 (HR 1.476, p = 0.010), preoperative biliary drainage (HR 1.372, p = 0.048), pathologic T2 stage (HR 2.188, p = 0.002) and T3, 4 stage (HR 3.178, p &amp;lt; 0.001) compared to T0, 1 stage, lymphovascular invasion (HR 2.087, p &amp;lt; 0.001), and adjuvant treatment (HR 0.243, p &amp;lt; 0.001) associated with OS. After PSM analysis, stages I (3YSR 76.8% vs 71.7%, p = 0.923), II (56.2% vs 46.6%, p = 0.886), and III (26.5% vs 31.4%, p = 0.856) exhibited no significant difference in OS between ypTNM and pTNM stages. Conclusions: Our study underscores comparable survival outcomes between ypTNM and pTNM stages in surgically resected pancreatic cancer, affirming the applicability of the TNM staging system after NAT. Consistent survival results, even following PSM analysis, highlight the reliability of TNM staging for guiding therapeutic decisions even in patients with NAT. Citation Format: Hyeong Seok Kim, Hochang Chae, Soo Yeun Lim, Hye Jeong Jeong, So Jeong Yoon, Sang Hyun Shin, In Woong Han, Jin Seok Heo, Hongbeom Kim. Stage-matched prognosis comparison between ypTNM and pTNM stage in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2399.

Abstract 5690: Urinary microRNA expression in pancreatic cancer with cachexia

Abstract Background: Cancer cachexia (CC) is a multifactorial syndrome characterized by appetite loss, weight loss and skeletal muscle wasting. It increases functional impairment, treatment-related toxicity, and a lower quality of life. Importantly, CC is one of the leading causes of cancer-related deaths, and its occurrence is particularly prevalent in advanced stages of pancreatic cancer (PC). The syndrome is thought to be associated with systemic inflammation and increased energy expenditure, yet the specific mechanisms remain to be fully understood. Although timely detection and intervention might be crucial in preventing CC’s progression, early diagnosis of this syndrome remains challenging due to the absence of suitable biomarkers. Here, we analyzed urinary microRNAs (miRNAs) as a potential noninvasive biomarkers for detecting CC in patients (pts) with PC. Methods: Clinical information including presence or absence of CC and urine samples were collected from pts with PC treated at National Cancer Center Hospital, Tokyo, Japan from March to October 2022. The diagnosis of CC was made according to the following definitions by Fearon. K et al. (1) weight loss of ≥5% within 6 months; (2) weight loss of ≥2% in pts with a BMI of &amp;lt;20 kg/m2; or (3) weight loss of ≥2% in pts with sarcopenia. In this study, pts who met the definition of CC within 6 months of enrollment were considered to have CC.Urinary miRNA profiles from pts with PC were sequenced by NGS and analyzed using DESeq2 to identify differentially expressed miRNAs (DEMs) between pts with CC and those without. DEMs were further explored for associated pathways and target genes using miRPathDB v.2.0. Results: Of the 64 subjects, 52 pts were included in the analysis after excluding three pts with low urine sample read coverage and nine pts with no information on CC status. Among those, 38 pts were classified as having CC. Patients’ background was as follows (CC/no CC); median age 70 [range: 44-80]/67 [57-74], male and female 19/7 pts, respectively, cStage {I (6/0), II (1/0), III (17/4), IV (14/10)} pts, median BMI (male 22.1 [17.7-27.2]/21.7 [18.2-28.2], female 21.7 [14.6-25.2]/21.9 [16.6-27.4]) kg/m2. Among 307 miRNAs detected in the urine of pts with PC, 49 miRNAs had previously been reported in CC research. The miR-141-5p was differentially expressed between pts with CC and those without CC (Wald test pBH = 0.079). It was down-regulated in pts with CC (Mann-Whitney U test p = 6.4e-4) and most significantly associated with the FoxO signaling pathway (ORA pBH = 1.84e-4), followed by the mTOR signaling pathway (ORA pBH = 0.008). Conclusions: Our study indicates that miR-141-5p holds potential as a noninvasive biomarker for the detection of CC in pts with PC. Although miR-141-5p has not been previously reported in CC, its significant association with the FoxO signaling pathway, which is one of the major pathways regulating skeletal muscle atrophy, underscores the relevance of miR-141-5p in the context of CC. Citation Format: Mao Okada, Shunsuke Kondo, Yukiko Igawa, Tatsuya Yoshida, Milos Havelka, Mika Mizunuma, Yuki Ichikawa, Noboru Yamamoto. Urinary microRNA expression in pancreatic cancer with cachexia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5690.

Abstract 5161: Integrating patient’s derived organoids and liquid biopsy: An exploratory study of early stage pancreatic cancer

Abstract Background: Pancreatic cancer (PC) has a 5-year survival of 12% despite recent therapeutic advancements. There is a desperate need to discover novel ways of treating PC since a large proportion of patients do not benefit from therapy and experience significant toxicity. A major cause of therapy failure is therapy resistance due to tumor heterogeneity. Nowadays, a deeper understanding of tumor heterogeneity could be assisted by the use of patients-derived organoids (PDOs). Furthermore, the use of liquid biopsy may allow for the investigation of circulating factors with predictive value and for disease monitoring over time. Methods: Patients were enrolled in the comprehensive, multiomic study of pancreatic cancer CONTAINER. Patients with early stage PC treated with preoperative chemotherapy or undergoing surgery first were selected for the present study. When possible, a surgical specimen was collected to obtain PDOs. Tissue from resected tumors was dissociated by GentleMACSTM dissociator (Miltenyi Biotec), fragments were embedded in MatrigelTMand cultured in PancreaCultTM human Organoid Media (stemcell technologies). PDO histological features were investigated by H&amp;E staining and IHC. Blood samples were collected before and one month after surgery. From blood samples circulating tumor cells (CTCs) were enriched and isolated, extracellular vesicles (EVs) were isolated from plasma with size-exclusion chromatography and their concentration and size distribution was evaluated with NanoSight NS300. Then, EV surface antigens were characterized by flow cytometry. A panel of inflammatory cytokines was finally evaluated through Ella Automated Immunoassay System. Results: In CONTAINER study 113 patients were enrolled and 30 of them underwent surgery. 21 surgical specimens were received from which 18 PDOs were successfully established. EVs with diameter ≥ 70nm were isolated from plasma, EV mean size was similar before and after surgery whereas individual variations in particle concentration and in surface antigen exposure were observed. Correlation with clinical and pathological characteristics of patients will be performed once reached an adequate sample size for statistical analyses. A panel of inflammatory cytokines (IL1β-, IFNγ, TNFα, IL6, IL8, TGFβ1, CRP and Leptin) was assessed in plasma samples obtained before and after surgery. Except for IL1β, a significant individual variation of circulating cytokines before and after surgery was observed. Conclusions: This study will contribute to unveil mechanisms of disease progression and drug resistance in PC. Possible predictive factors and mechanisms of drug resistance will be investigated taking advantage of the information derived from both in vitro models and circulating tumor-related entities. Citation Format: Michela Cortesi, Tania Rossi, Michele Zanoni, Sara Bandini, Carlo Alberto Pacilio, Alessandro Cucchetti, Martina Valgiusti, Chiara Gallio, Alessandro Passardi, Giorgia Gurioli, Sara Bravaccini, Alessandra Dubini, Giovanni Luca Frassineti, Paola Ulivi, Giovanni Martinelli, Giorgio Ercolani, Ilario Giovanni Rapposelli. Integrating patient’s derived organoids and liquid biopsy: An exploratory study of early stage pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5161.

Abstract 7134: Treatment of pancreatic cancer cells with tumor treating fields (TTFields) and PARP inhibitors

Abstract Background: Therapeutic options for advanced stage pancreatic cancer are limited. Patients harboring germline BRCA mutations benefit from PARP inhibitors (PARPi); unfortunately, such mutations are rare in pancreatic cancer. Tumor Treating Fields (TTFields), electric fields that disrupt cellular processes crucial for cancer cell viability, have shown effectiveness against pancreatic cancer cells, and are currently under clinical investigation for the treatment of patients with pancreatic cancer. The mechanism of action of TTFields in various cancer types has suggested involvement of BRCA downregulation. The current study examined the potential sensitization of BRCA wild-type pancreatic cancer cell lines to PARPi with TTFields application. Methods: BxPC3 and AsPC1 human pancreatic BRCA wild-type cancer cells were treated for 72 h with TTFields (frequency of 150 kHz; intensity of 1 and 0.5 V/cm RMS, respectively), using the inovitro device. The PARPi niraparib and olaparib were each administered to the cells at various concentrations, with or without co-application of TTFields. At treatment cessation, cell count, colony formation, and apoptosis were measured. Results: Applying PARPi to pancreatic cell lines yielded a dose-dependent cytotoxic and anti-clonogenic effects, and induced apoptosis. TTFields application also induced such effects when applied alone, while delivery of TTFields together with PARPi amplified the effects demonstrated by PARPi alone. Conclusions: Concomitant application of TTFields and PARPi in BRCA wild type pancreatic cancer cells exhibits a potential improvement relative to the mono-therapies. This could be rationalized based on the previously demonstrated ability of TTFields to induce a state of BRCAness in cancer cells, and suggests benefit for TTFields and PARPi co-treatment in the absence of background BRCA mutations. Citation Format: Hila Ene, Kerem Ben Meir, Antonia Martinez-Conde, Roni Frechtel-Gerzi, Hila Gabay, Daria Gerasimova, Rotem Engelman, Eyal Dor-On, Adi Haber, Moshe Giladi, Yoram Palti. Treatment of pancreatic cancer cells with tumor treating fields (TTFields) and PARP inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7134.