Early Detection Of Pancreatic Cancer Research Articles

Letter to the editor "Inflammatory biomarkers and nanotechnology: new insights in pancreatic cancer early detection".

Letter to the editor "Inflammatory biomarkers and nanotechnology: new insights in pancreatic cancer early detection".

Unveiling liquid markers: The diagnostic revolution in early detection of pancreatic cancer through liquid biopsy

Unveiling liquid markers: The diagnostic revolution in early detection of pancreatic cancer through liquid biopsy

Multiscale and multiperception feature learning for pancreatic lesion detection based on noncontrast CT

Background. Pancreatic cancer is one of the most malignant tumours, demonstrating a poor prognosis and nearly identically high mortality and morbidity, mainly because of the difficulty of early diagnosis and timely treatment for localized stages. Objective. To develop a noncontrast CT (NCCT)-based pancreatic lesion detection model that could serve as an intelligent tool for diagnosing pancreatic cancer early, overcoming the challenges associated with low contrast intensities and complex anatomical structures present in NCCT images. Approach. We design a multiscale and multiperception (MSMP) feature learning network with ResNet50 coupled with a feature pyramid network as the backbone for strengthening feature expressions. We added multiscale atrous convolutions to expand different receptive fields, contextual attention to perceive contextual information, and channel and spatial attention to focus on important channels and spatial regions, respectively. The MSMP network then acts as a feature extractor for proposing an NCCT-based pancreatic lesion detection model with image patches covering the pancreas as its input; Faster R-CNN is employed as the detection method for accurately detecting pancreatic lesions. Main results. By using the new MSMP network as a feature extractor, our model outperforms the conventional object detection algorithms in terms of the recall (75.40% and 90.95%), precision (40.84% and 68.21%), F1 score (52.98% and 77.96%), F2 score (64.48% and 85.26%) and Ap50 metrics (53.53% and 70.14%) at the image and patient levels, respectively. Significance.The good performance of our new model implies that MSMP can mine NCCT imaging features for detecting pancreatic lesions from complex backgrounds well. The proposed detection model is expected to be further developed as an intelligent method for the early detection of pancreatic cancer.

Pancreatic cancer: from early detection to personalized treatment approaches.

Pancreatic cancer is notorious for its persistently poor prognosis and health outcomes, so some of the questions that may be begged are "Why is it mostly diagnosed at end stage?", "What could we possibly do with the advancing technology in today's world to detect early pancreatic cancer and intervene?", and "Are there any implementation of the existing novel imaging technologies?". Well, to start with, this is in part because the majority of patients presented would already have reached a locally advanced or metastatic stage at the time of diagnosis due to its highly aggressive characteristics and lack of symptoms. Due to this striking disparity in survival, advancements in early detection and intervention are likely to significantly increase patients' survival. Presently, screening is frequently used in high-risk individuals in order to obtain an early pancreatic cancer diagnosis. Having a thorough understanding of the pathogenesis and risk factors of pancreatic cancer may enable us to identify individuals at high risk, diagnose the disease early, and begin treatment promptly. In this review, the authors outline the clinical hurdles to early pancreatic cancer detection, describe high-risk populations, and discuss current screening initiatives for high-risk individuals. The ultimate goal of this current review is to study the roles of both traditional and novel imaging modalities for early pancreatic cancer detection. A lot of the novel imaging techniques mentioned seem promising, but they need to be put to the test on a large scale and may need to be combined with other non-invasive biomarkers before they can be widely used.

The role of biomarkers in the early detection of pancreatic cancer.

Pancreatic surveillance can detect early-stage pancreatic cancer and achieve long-term survival, but currently involves annual endoscopic ultrasound and MRI/MRCP, and is recommended only for individuals who meet familial/genetic risk criteria. To improve upon current approaches to pancreatic cancer early detection and to expand access, more accurate, inexpensive, and safe biomarkers are needed, but finding them has remained elusive. Newer approaches to early detection, such as using gene tests to personalize biomarker interpretation, and the increasing application of artificial intelligence approaches to integrate complex biomarker data, offer promise that clinically useful biomarkers for early pancreatic cancer detection are on the horizon.

The high FKBP1A expression in WBCs as a potential screening biomarker for pancreatic cancer

Given the limitation of current routine approaches for pancreatic cancer screening and detection, the mortality rate of pancreatic cancer cases is still critical. The development of blood-based molecular biomarkers for pancreatic cancer screening and early detection which provide less-invasive, high-sensitivity, and cost-effective, is urgently needed. The goal of this study is to identify and validate the potential molecular biomarkers in white blood cells (WBCs) of pancreatic cancer patients. Gene expression profiles of pancreatic cancer patients from NCBI GEO database were analyzed by CU-DREAM. Then, mRNA expression levels of three candidate genes were determined by quantitative RT-PCR in WBCs of pancreatic cancer patients (N = 27) and healthy controls (N = 51). ROC analysis was performed to assess the performance of each candidate gene. A total of 29 upregulated genes were identified and three selected genes were performed gene expression analysis. Our results revealed high mRNA expression levels in WBCs of pancreatic cancer patients in all selected genes, including FKBP1A (p < 0.0001), PLD1 (p < 0.0001), and PSMA4 (p = 0.0002). Among candidate genes, FKBP1A mRNA expression level was remarkably increased in the pancreatic cancer samples and also in the early stage (p < 0.0001). Moreover, FKBP1A showed the greatest performance to discriminate patients with pancreatic cancer from healthy individuals than other genes with the 88.9% sensitivity, 84.3% specificity, and 90.1% accuracy. Our findings demonstrated that the alteration of FKBP1A gene in WBCs serves as a novel valuable biomarker for patients with pancreatic cancer. Detection of FKBP1A mRNA expression level in circulating WBCs, providing high-sensitive, less-invasive, and cost-effective, is simple and feasible for routine clinical setting that can be applied for pancreatic cancer screening and early detection.

The Pancreatic Cancer Early Detection (PRECEDE) Study is a Global Effort to Drive Early Detection: Baseline Imaging Findings in High-Risk Individuals.

Pancreatic adenocarcinoma (PC) is a highly lethal malignancy with a survival rate of only 12%. Surveillance is recommended for high-risk individuals (HRIs), but it is not widely adopted. To address this unmet clinical need and drive early diagnosis research, we established the Pancreatic Cancer Early Detection (PRECEDE) Consortium. PRECEDE is a multi-institutional international collaboration that has undertaken an observational prospective cohort study. Individuals (aged 18-90 years) are enrolled into 1 of 7 cohorts based on family history and pathogenic germline variant (PGV) status. From April 1, 2020, to November 21, 2022, a total of 3,402 participants were enrolled in 1 of 7 study cohorts, with 1,759 (51.7%) meeting criteria for the highest-risk cohort (Cohort 1). Cohort 1 HRIs underwent germline testing and pancreas imaging by MRI/MR-cholangiopancreatography or endoscopic ultrasound. A total of 1,400 participants in Cohort 1 (79.6%) had completed baseline imaging and were subclassified into 3 groups based on familial PC (FPC; n=670), a PGV and FPC (PGV+/FPC+; n=115), and a PGV with a pedigree that does not meet FPC criteria (PGV+/FPC-; n=615). One HRI was diagnosed with stage IIB PC on study entry, and 35.1% of HRIs harbored pancreatic cysts. Increasing age (odds ratio, 1.05; P<.001) and FPC group assignment (odds ratio, 1.57; P<.001; relative to PGV+/FPC-) were independent predictors of harboring a pancreatic cyst. PRECEDE provides infrastructure support to increase access to clinical surveillance for HRIs worldwide, while aiming to drive early PC detection advancements through longitudinal standardized clinical data, imaging, and biospecimen captures. Increased cyst prevalence in HRIs with FPC suggests that FPC may infer distinct biological processes. To enable the development of PC surveillance approaches better tailored to risk category, we recommend adoption of subclassification of HRIs into FPC, PGV+/FPC+, and PGV+/FPC- risk groups by surveillance protocols.

Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank

Metabolomics for early pancreatic cancer detection in plasma samples from a Swedish prospective population-based biobank

Abstract 6165: Early detection of pancreatic cancer by hyperpolarized magnetic resonance

Abstract Introduction: Pancreatic cancer is difficult to diagnose due to its asymptomatic presentation at early stages. Therefore, there is an unmet need for non-invasive imaging markers that can help identify the aggressive pancreatic lesions at an early time point. One of the most promising imaging biomarkers is the conversion of hyperpolarized (HP) pyruvate to lactate1-3. With HP metabolic imaging, the conversion will be monitored among different premalignant models at different timepoints as well as tested against pancreatitis, a known confounder of pancreatic cancer in the clinic. Methods: HP [1-13C]pyruvate Magnetic Resonance Spectroscopy (MRS) was employed to study the metabolic processes in tamoxifen inducible genetically engineered mouse models (P48CreERT2;LSL-KrasG12D(iKC)) with pre-invasive pancreatic intraepithelial neoplasia (PanIN) precursor lesions, invasive pancreatic cancer model (P48CreERT2;LSL-KrasG12D; LSL-p53R172H (iKPC)) and control animals (P48CreERT2 (iC)) at 7T Bruker MRI scanner. These mice were imaged before tamoxifen induction at 10-, 20-, and 30-weeks post induction. For the pancreatitis model, iC and iKC mice they were treated with caerulein for three weeks, 7 weeks after tamoxifen induction. The pancreatitis mice were imaged 24 hours after the last caerulein injection. Results/Discussion: HP lactate-to-pyruvate ratio is increased in the cancer models compared to the control model. In the iKPC mouse model, at the 20-week post induction imaging there was a significant increase of the lactate-to-pyruvate ratio compared to the 10-weektime point after induction. The 20-week iKPC time point ratio compared to the iKC and control mouse models was significantly higher, indicating the aggressive nature of the disease. Even in the iKC model there is a slight increase of the lactate-to-pyruvate ratio at 20-weeks post induction compared to both previous time points, pre-induction and 10-week. No change in the lactate-to-pyruvate ratio was not observed with the pancreatitis phenotype. In the future, we plan on imaging at earlier timepoints or at smaller intervals in the iKPC model, to observe the exact moment the metabolism switches to lactate. Conclusion: Our data demonstrates that the metabolic flux to lactate is only increasing in the premalignant models of pancreatic cancer but not in the pancreatitis model, suggesting that the differentiation between early pancreatic cancer and pancreatitis can be achieved by hyperpolarized metabolic imaging. We are currently in the process of translating this in a clinical trial at MD Anderson Cancer Center. Citation Format: Paytience L. Smith, José S. Enriquez, Rian Howell, Olivereen Le Roux, Shivanand Pudakalakatti, Prasanta Dutta, Florencia Mcallister, Pratip Bhattacharya. Early detection of pancreatic cancer by hyperpolarized magnetic resonance [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 6165.

Abstract 6091: Multi-cancer early cancer detection and cancer-type identification with high sensitivity non-invasive using urine: Pancreatic lung cancer early detection

Abstract N-NOSE, a breakthrough cancer detection test from HIROTSU BIO SCIENCE, utilizes the unique chemotactic behavior of the nematode C. elegans. This nematode is drawn to the urine of individuals with 15 different types of cancers (including stomach, colon-rectum, lung, breast, pancreas, liver, prostate, uterus, esophagus, gallbladder, bile duct, kidney, urinary bladder, ovary, oropharynx) while avoiding urine from healthy persons, making N-NOSE a comprehensive primary screening tool. It has a high accuracy rate, with 87.5% sensitivity and 90.2% specificity for early-stage cancers. Being non-invasive and reasonably priced, N-NOSE has been a significant success in Japan since its 2020 launch, with over 500,000 screenings.This presentation delves into the technology aspect of N-NOSE in Japan, comparing its clinical research and key findings with competitors to underscore its effectiveness in early cancer detection. Furthermore, N-NOSE now advances to not only detect cancer but also identify its type in a noninvasive way, using urine and with high PPV.With pancreatic cancer being particularly lethal, we outline “N-NOSE plus pancreas,” the world’s first pancreatic cancer detection test at an early stage. This involves genetically modifying C. elegans to react specifically to early-stage pancreatic cancer urine samples, a development centered on the newly identified cr-4 GPCR in AWC neurons. Next, we profile our newest liver-cancer-specific test, “N-NOSE plus liver,” which offers early liver cancer detection with high sensitivity and specificity using urine.Finally, we highlight how N-NOSE bridges the gap in cancer screening and type identification, offering a complete, non-invasive solution. Citation Format: Eric Di Luccio, Takaaki Hirotsu. Multi-cancer early cancer detection and cancer-type identification with high sensitivity non-invasive using urine: Pancreatic lung cancer early detection [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 6091.

Molecular Pathology of Pancreatic Cystic Lesions with a Focus on Malignant Progression.

The malignant progression of pancreatic cystic lesions (PCLs) remains understudied with a knowledge gap, yet its exploration is pivotal for effectively stratifying patient risk and detecting cancer at its earliest stages. Within this review, we delve into the latest discoveries on the molecular level, revealing insights into the IPMN molecular landscape and revised progression model, associated histologic subtypes, and the role of inflammation in the pathogenesis and malignant progression of IPMN. Low-grade PCLs, particularly IPMNs, can develop into high-grade lesions or invasive carcinoma, underscoring the need for long-term surveillance of these lesions if they are not resected. Although KRAS and GNAS remain the primary oncogenic drivers of neoplastic development in IPMNs, additional genes that are important in tumorigenesis have been recently identified by whole exome sequencing. A more complete understanding of the genes involved in the molecular progression of IPMN is critical for effective monitoring to minimize the risk of malignant progression. Complicating these strategies, IPMNs are also frequently multifocal and multiclonal, as demonstrated by comparative molecular analysis. Algorithms for preoperative cyst sampling and improved radiomic techniques are emerging to model this spatial and temporal genetic heterogeneity better. Here, we review the molecular pathology of PCLs, focusing on changes associated with malignant progression. Developing models of molecular risk stratification in PCLs which can complement radiologic and clinical features, facilitate the early detection of pancreatic cancer, and enable the development of more personalized surveillance and management strategies are summarized.

N-glycan biosignatures as a potential diagnostic biomarker for early-stage pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of less than 10%, owing to its late-stage diagnosis. Early detection of pancreatic cancer (PC) can significantly increase survival rates. To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan analysis. An extensive patient cohort was used to determine a biomarker signature, including patients with PDAC that was well-defined at an early stage (stages I and II). The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I, 22 with stage II, 4 with stage III, 16 with stage IV PDAC, and 88 controls. We used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan signature-based diagnosis model called the "Glyco-model". The biomarker signature was created to discriminate samples derived from patients with PC from those of controls, with a receiver operating characteristic area under the curve of 0.86. In addition, the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls, with a receiver operating characteristic area under the curve of 0.919. Glyco-model demonstrated favorable diagnostic performance in all stages of PC. The diagnostic sensitivity for stage I PDAC was 89.66%. In a prospective validation study, this serum biomarker signature may offer a viable method for detecting early-stage PDAC.

Development of a Serum-Based MicroRNA Signature for Early Detection of Pancreatic Cancer: A Multicenter Cohort Study

BackgroundA grim prognosis of pancreatic cancer (PCa) was attributed to the difficulty in early diagnosis of the disease.AimsIdentifying novel biomarkers for early detection of PCa is thus urgent to improve the overall survival rates of patients.MethodsThe study was performed firstly by identification of candidate microRNAs (miRNAs) in formalin-fixed, paraffin-embedded tissues using microarray profiles, and followed by validation in a serum-based cohort study to assess clinical utility of the candidates. In the cohorts, a total of 1273 participants from four centers were retrospectively recruited as two cohorts including training and validation cohort. The collected serum specimens were analyzed by real-time polymerase chain reaction.ResultsWe identified 27 miRNAs expressed differentially in PCa tissues as compared to the benign. Of which, the top-four was selected as a panel whose diagnostic efficacy was fully assessed in the serum specimens. The panel exhibited superior to CA19-9, CA125, CEA and CA242 in discriminating patients with early stage PCa from healthy controls or non-PCa including chronic pancreatitis as well as pancreatic cystic neoplasms, with the area under the curves (AUC) of 0.971 (95% CI 0.956–0.987) and 0.924 (95% CI 0.899–0.949), respectively. Moreover, the panel eliminated interference from other digestive tumors with a specificity of 90.2%.ConclusionsA panel of four serum miRNAs was developed showing remarkably discriminative ability of early stage PCa from either healthy controls or other pancreatic diseases, suggesting it may be developed as a novel, noninvasive approach for early screening of PCa in clinic.Graphical

Simulating the healthcare workforce impact and capacity for pancreatic cancer care in Victoria: a model-based analysis

BackgroundThe incidence of pancreatic cancer is rising. With improvements in knowledge for screening and early detection, earlier detection of pancreatic cancer will continue to be more common. To support workforce planning, our aim is to perform a model-based analysis that simulates the potential impact on the healthcare workforce, assuming an earlier diagnosis of pancreatic cancer.MethodsWe developed a simulation model to estimate the demand (i.e. new cases of pancreatic cancer) and supply (i.e. the healthcare workforce including general surgeons, medical oncologists, radiation oncologists, pain medicine physicians, and palliative care physicians) between 2023 and 2027 in Victoria, Australia. The model compares the current scenario to one in which pancreatic cancer is diagnosed at an earlier stage. The incidence of pancreatic cancer in Victoria, five-year survival rates, and Victoria’s population size were obtained from Victorian Cancer Registry, Cancer Council NSW, and Australian Bureau of Statistics respectively. The healthcare workforce data were sourced from the Australian Government Department of Health and Aged Care’s Health Workforce Data. The model was constructed at the remoteness level. We analysed the new cases and the number of healthcare workforce by profession together to assess the impact on the healthcare workforce.ResultsIn the status quo, over the next five years, there will be 198 to 220 stages I-II, 297 to 330 stage III, and 495 to 550 stage IV pancreatic cancer cases diagnosed annually, respectively. Assuming 20–70% of the shift towards pancreatic cancer’s earlier diagnosis (shifting from stage IV to stages I-II pancreatic cancer within one year), the stages I-II cases could increase to 351 to 390 or 598 to 665 per year. The shift to early diagnosis led to substantial survival gains, translating into an additional 284 or 795 out of 5246 patients with pancreatic cancer remaining alive up to year 5 post-diagnosis. Workforce supply decreases significantly by the remoteness levels, and remote areas face a shortage of key medical professionals registered in delivering pancreatic cancer care, suggesting travel necessities by patients or clinicians.ConclusionImproving the early detection and diagnosis of pancreatic cancer is expected to bring significant survival benefits, although there are workforce distribution imbalances in Victoria that may affect the ability to achieve the anticipated survival gain.

Inhibition of the Alternative Complement Pathway May Cause Secretion of Factor B, Enabling an Early Detection of Pancreatic Cancer.

This study aims to elucidate the cellular mechanisms behind the secretion of complement factor B (CFB), known for its dual roles as an early biomarker for pancreatic ductal adenocarcinoma (PDAC) and as the initial substrate for the alternative complement pathway (ACP). Using parallel reaction monitoring analysis, we confirmed a consistent ∼2-fold increase in CFB expression in PDAC patients compared with that in both healthy donors (HD) and chronic pancreatitis (CP) patients. Elevated ACP activity was observed in CP and other benign conditions compared with that in HD and PDAC patients, suggesting a functional link between ACP and PDAC. Protein-protein interaction analyses involving key complement proteins and their regulatory factors were conducted using blood samples from PDAC patients and cultured cell lines. Our findings revealed a complex control system governing the ACP and its regulatory factors, including Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, adrenomedullin (AM), and complement factor H (CFH). Particularly, AM emerged as a crucial player in CFB secretion, activating CFH and promoting its predominant binding to C3b over CFB. Mechanistically, our data suggest that the KRAS mutation stimulates AM expression, enhancing CFH activity in the fluid phase through binding. This heightened AM-CFH interaction conferred greater affinity for C3b over CFB, potentially suppressing the ACP cascade. This sequence of events likely culminated in the preferential release of ductal CFB into plasma during the early stages of PDAC. (Data set ID PXD047043.).

Clinical development of a blood biomarker using apolipoprotein-A2 isoforms for early detection of pancreatic cancer

BackgroundWe have previously reported apolipoprotein A2-isoforms (apoA2-is) as candidate plasma biomarkers for early-stage pancreatic cancer. The aim of this study was the clinical development of apoA2-is.MethodsWe established a new enzyme-linked immunosorbent sandwich assay for apoA2-is under the Japanese medical device Quality Management System requirements and performed in vitro diagnostic tests with prespecified end points using 2732 plasma samples. The clinical equivalence and significance of apoA2-is were compared with CA19-9.ResultsThe point estimate of the area under the curve to distinguish between pancreatic cancer (n = 106) and healthy controls (n = 106) was higher for apoA2-ATQ/AT [0.879, 95% confidence interval (CI): 0.832–0.925] than for CA19-9 (0.849, 95% CI 0.793–0.905) and achieved the primary end point. The cutoff apoA2-ATQ/AT of 59.5 μg/mL was defined based on a specificity of 95% in 2000 healthy samples, and the reliability of specificities was confirmed in two independent healthy cohorts as 95.3% (n = 106, 95% CI 89.4–98.0%) and 95.8% (n = 400, 95% CI 93.3–97.3%). The sensitivities of apoA2-ATQ/AT for detecting both stage I (47.4%) and I/II (50%) pancreatic cancers were higher than those of CA19-9 (36.8% and 46.7%, respectively). The combination of apoA2-ATQ/AT (cutoff, 59.5 μg/mL) and CA19-9 (37 U/mL) increased the sensitivity for pancreatic cancer to 87.7% compared with 69.8% for CA19-9 alone. The clinical performance of apoA2-is was blindly confirmed by the National Cancer Institute Early Detection Research Network.ConclusionsThe clinical performance of ApoA2-ATQ/AT as a blood biomarker is equivalent to or better than that of CA19-9.

Abstract C011: Detection of circulating tumor cells for the early detection of pancreatic cancer

Abstract Introduction The majority of pancreatic cancer patients are diagnosed with advanced, metastatic disease. Biomarkers to detect pancreatic cancer at earlier stages could drastically improve the poor survival rates. Circulating tumor cells (CTCs) are tumor cells that disseminate or are shed into the vascular system and have been detected in patients at pre-malignant stages. However, detecting these rare cells accurately and reliably remains a challenge. The AccuCyte-CyteFinder system uses density-based enrichment of blood nucleated cells followed by detection of CTCs using fluorescence staining, whole slide scanning and automated image analysis. This study aimed to examine whether CTCs could be used to identify patients with pancreatic lesions likely to malignant. Methods 50 patients undergoing an endoscopic ultrasound procedure for a pancreatic mass were recruited at the Royal Prince Alfred Hospital, Sydney, Australia or Chris O’Brien Lifehouse, Sydney, Australia. Peripheral blood was collected prior to the procedure and processed for CTCs on the AccuCyte-CyteFinder platform using a CK+ EpCAM+ CD45- staining panel. Results 28% (14/50) were found to have an intraductal papillary mucinous neoplasm (IPMN), 10% (5/50) pancreatic ductal adenocarcinoma (PDAC), 6% (3/50) pancreatic neuroendocrine tumor (PNET), 42% (21/50) non-neoplastic pancreatic cyst, and 14% (7/50) normal (no mass found). CTCs were highest in the PDAC group with an average of 5 cells/ml, followed by the IPMN (3 cells/ml), pancreatic cyst (2.5 cells/ml), and PNET (0 cells/ml). 86% (12/14) of IPMN patients had detectable CTCs. 2 IPMN patients with CTC counts of more than 5 cells/ml resulted in a resected sample having high-grade dysplasia while 3 IPMN patients with no/low CTC counts resulted in a resected sample having low-grade dysplasia. There was no correlation with the size of the pancreatic mass and CTC number. Conclusions CTCs could be detected in patients with pre-malignant pancreatic cancer and could determine malignancy. CTCs could potentially be used to detect pancreatic cancer early however, larger patient numbers and longer follow-up are required to validate these findings. Citation Format: Dannel Yeo, Vera Klemm, Payal Saxena, Althea Bastian, Heidi Strauss, Charbel Sandroussi, Sara Wahlroos, Peter Grimison, John E.J. Rasko. Detection of circulating tumor cells for the early detection of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C011.

Abstract C006: Combining the methylation and gene expression contiguous signals leads to better pancreatic cancer patient stratification and early detection

Abstract Background Pancreatic cancer (PAC) lacks methods for screening, patient stratification, resulting in late diagnosis and inadequate treatment of patients. Cell-free DNA (cfDNA) methylation patterns are signals representing real-time cancer characteristics such as early presence, tissue, and cell of origin. The aim of this study is to provide a better patient stratification based on differential patterns on the combined methylation and gene expression results in PAC and normal samples and provide proof-of-concept for early detection. Method Differential methylation region (DMR) analysis was performed on 180 TCGA PAAD and normal tissue samples using paired methylation and expression data. Validation was done on 143 Infiltrating duct carcinomas (IDC), (stage I, II, II), and 4 normal samples and the 4 probe clusters (FPC) were defined based on their methylation status: HM = high methylation, IM = intermediate methylation, LM = low methylation and MM = minimum methylation. 3-year and 5-year survival analysis with Kaplan-Meier was done. Gene ontology (GO) and Biological Pathway analyses (PA) were performed on DMRs of FPC. Integration analysis on paired methylation and expression data and the limma analysis was performed for significant genes in 5000 bp vicinities of the selected DMRs. Finally, selected 23 DMRs, were targeted in plasma cfDNA from 9 PAC patients (stage I-III) and 20 matching control samples. Results The survival analysis of FPC, shows the highest probability difference between HM and MM groups with p-values of 0.018 and 0.029 for 3-year and 5-year survival, respectively. Variability analysis shows 5740 significant CpG sites and 1135 significant DMRs comparing IDC tumor samples to controls. GO and PA on DRMs of FPC, indicated the most PAC specific pathways in the group of probes with MM status. Integration analysis on the methylation and mutation data of the selected genes of GO analysis shows potential to discriminate between normal and PAC patients and in between HM and MM groups and showed smaller mutation burden in MM and LM sample groups. Comparing MM to HM groups of patients, shows the highest significance in 5 downregulated genes in 5000 bp vicinity from Hypermethylated probes and 13 upregulated genes and 425 regions in 5000 base pairs vicinity from 170 hypomethylated probes. Survival analysis on the selected genes showed a very high correlation between the expression of the genes like SIX2, DNMT3A, ZFP91 and POR and the survival probability on FPC. Additionally, it has been shown that the selected DMRs, show good individual performance of AUC &amp;gt;0.95 in the in-house analysis of plasma cfDNA targeted data from 9 PAC patients (stage I-III) and 20 matching control samples. Conclusion Methylation markers carry distinct biological signals and combined with gene expression differentiate the PAC patient groups, showing potential of the methylation signals for better patient stratification outcomes for improved survival. High accuracy for cancer detection was observed for early-stage cancers when compared to cfDNA from matching controls. Citation Format: Pardis Saadatmand, Urban Kunej, Kristi Kruusmaa. Combining the methylation and gene expression contiguous signals leads to better pancreatic cancer patient stratification and early detection [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C006.

Comparison of different Pancreatic cancer treatments: a three-year retrospective study in the oncology center of Tangier university hospital, Morocco

BackgroundPancreatic cancer is among the most lethal malignancies, with a 5-year overall survival (OS) of less than 10% for all stages. The present study aims to evaluate the epidemiological and clinical characteristics, as well as the results of different treatments of patients diagnosed and treated between 2019 and 2021 in the Oncology Center of Tangier, University Hospital, Morocco.MethodsTo compare the evolution of the pancreatic cancer between the different chemotherapy regimens, a retrospective study was performed using data collected over a period of 3 years. For each patient, the data were described and statistically analyzed in the dedicated operating sheet.Results55 pancreatic cancer patients were included in this study, and the median follow up was 3 months. The mean age of patients was 59.5 ± 10.3 years (extremes 34–79) and the sex ratio male/female was 0.9. Most patients were diagnosed with adenocarcinoma (92.3%), but metastatic stage was the most frequent (56.4%). The surgery was applied to 16.36% of patients. 10.9% of patients have received adjuvant chemotherapy and 76.4% received palliative chemotherapy. Chemotherapy regimens included mainly Gemcitabine and Folfirinox. The median OS was significantly longer for patients treated with Folfirinox versus Gemcitabine (6 months versus 3 months, p-value < 0.016). The median OS for patients that received Folfirinox and Gemcitabine successively (19.7 months) was significantly longer compared to patients that received a monotherapy with either Folfirinox or Gemcitabine alone (p-value < 0.016).ConclusionThese findings reinforce the use of advanced methods for earlier detection of pancreatic cancer and the development of effective immunotherapies or more targeted therapies.

P-164 - Preparation and evaluation of an ADAM8-targeted 111In-labeled antibody for the detection of early pancreatic cancer

P-164 - Preparation and evaluation of an ADAM8-targeted 111In-labeled antibody for the detection of early pancreatic cancer