Staging Of Pancreatic Cancer Research Articles

P-P58 The role of PET-CT in the management of pancreatic cancer. A Northern Ireland experience

BackgroundDiagnosis and staging has proven to be difficult in 10-20% of patients with pancreatic cancer. The PET-PANC study found that PET-CT significantly influenced the staging and management of pancreatic cancer and therefore the NICE guidelines now advise PET-CT in all patients who have localised potentially resectable disease. This study aimed to investigate the impact of PET-CT on the management of pancreatic cancer patients in a single tertiary referral centre.MethodsThere were 288 patients with pancreatic cancer discussed at the Northern Ireland Regional Hepatobiliary MDM from January 2020 to March 2021. Of these patients, 176 were deemed to have inoperable disease based on initial CT, 5 had borderline resectable disease, 1 had holding chemotherapy due to COVID restrictions and 57 were excluded from surgical resection for a variety of reasons. These included the patient being unfit for surgery, the patient declining operative intervention and an alternative treatment offered as result of COVID-19 pandemic. Therefore, there were 49 patients with pancreatic adenocarcinoma which the MDT concluded should be considered for surgical resection.ResultsA total of 27 patients who were due to undergo a curative resection had a pre-operative PET-CT scan (55.1%). This demonstrated metastatic disease in 9 cases (33.3%). Four patients who did not have a preoperative PET-CT were found to have metastatic disease at operation (9.7%). This equated to a total metastatic incidence of 26.5% in those who had been initially deemed resectable based on CT scan alone. The time interval from MDM decision to surgery averaged 25.4 days in those who did not have a PET/CT compared to 40.43 days in those who did. This was an average delay of 15.07 days until treatment.ConclusionsThis study demonstrates the important role the PET-CT has in the management of patients with pancreatic cancer. A significant number of patients avoided an unnecessary operation which would have delayed the commencement of chemotherapy. However, there are limitations to PET-CT, demonstrated in the patient with an inconclusive result, who was found to have liver metastases at surgery. The introduction of PET-CT in the staging process does undoubtedly cause delays to surgical resection and a more streamlined pathway needs to be developed to limit the delay to curative treatment.

O-P09 PACT-UK: PAncreatic Cancer reporting Template - a national pan-specialty collaborative consensus project to develop a standardised radiological reporting proforma for pancreatic cancer

Abstract Background In line with the NCRI framework, appropriate staging and classification of pancreatic cancer, with particular relevance to vascular involvement, is essential to ensure patients are offered all potential treatment options both at diagnosis and post-neoadjuvant therapy. This pan-specialty national collaborative consensus project, supported by PCUK,AUGIS,PSGBI,RCSEng,NCRI,RCR and BSGAR, aimed to develop a succinct radiological reporting template to allow a more consistent and standardized means of detailing all clinically-relevant aspects of pancreatic cancer, which, in addition to the aforementioned benefits, will allow more efficient MDT review, improved ability to audit national practice, and optimized clinical trial design. Methods In stage one, a core group of stakeholders from surgery, radiology and oncology was formed to establish current practice and determine the optimal data-set for a template. This included a blinded radiological validation study of established templates in use (Beth-Israel, PROTRACT and Glasgow proformas), and national survey of consultant surgeons on the PSGBI mailing list. Thereafter, consensus meetings led to the development of a provisional template. In stage two, representatives from surgery, radiology and oncology at all UK HPB units attended a consensus meeting to discuss and finalise the first official template draft, with subsequent trial utilisation in clinical practice. Results In stage one, the radiological assessment highlighted a significant variation in reporting of vascular involvement, with 100% concordance in only 30% of cases. Within the surgeon survey, amongst various tumour-related factors, most notably a significant majority preferred a specific range of degrees of vascular involvement, and specific information regarding tributary involvement and associated narrowing/occlusion/thrombosis. Both processes, and subsequent national consensus meetings in stage two, helped establish the ideal factors required in a template with respect to usability, clinical relevance, applicability and IT-factors, resulting in the generation of the PACT-UK proforma that will be presented at the congress. Conclusions This pan-specialty collaborative consensus project has successfully produced the first nationally-developed pancreatic cancer radiological reporting template. In stage three, the PACT-UK group aim to continue trialing the proforma nationally, with upcoming workshops facilitated by RCR/BSGAR to ensure buy-in from radiologists at all HPB units. Further representation from all units is welcomed, with the philosophy that template data-points can and will continue to evolve on the basis of ongoing feedback from consensus meetings, and following the development of more aggressive surgical techniques and novel neoadjuvant therapies. Plans for the use of PACT-UK within national audit and clinical trials is under-way.

Additional MRI more effective for initial staging in pancreatic cancer than standard imaging and less costly

Additional MRI more effective for initial staging in pancreatic cancer than standard imaging and less costly

Are Circulating Immune Cells a Determinant of Pancreatic Cancer Risk? A Prospective Study Using Epigenetic Cell Count Measures.

Evidence is accumulating that immune cells play a prominent role in pancreatic cancer etiology but prospective investigations are missing. We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study with 502 pairs of incident pancreatic cancer cases and matched controls. Relative counts of circulating immune cells (neutrophils and lymphocyte sublineages: total CD3+, CD8+, CD4+, and FOXP3+ regulatory T cells (Tregs) relative to nucleated cells, (white blood cells) were measured by qRT-PCR. ORs with 95% confidence intervals were estimated using logistic regressions, modeling relative counts of immune cells on a continuous scale. Neither relative counts of immune cell types taken individually, nor mutually adjusted for each other were associated with pancreatic cancer risks. However, in subgroup analyses by strata of lag-time, higher relative counts of Tregs and lower relative counts of CD8+ were significantly associated with an increased pancreatic cancer risks in participants diagnosed within the first 5 years of follow-up. These results might reflect reverse causation, due to higher relative counts of Tregs and lower counts of CD8+ cells among individuals with more advanced stages of latent pancreatic cancer, who are closer to the point of developing clinical manifest disease. We have shown, for the first time, that increased relative counts of regulatory T cells and lower relative counts of CD8+, cytotoxic T cells may be associated with pancreatic cancer risk or relatively late-stage tumor development.See related commentary by Michaud and Kelsey, p. 2176.

Additional MRI for initial M-staging in pancreatic cancer: a cost-effectiveness analysis

ObjectivePancreatic cancer is portrayed to become the second leading cause of cancer-related death within the next years. Potentially complicating surgical resection emphasizes the importance of an accurate TNM classification. In particular, the failure to detect features for non-resectability has profound consequences on patient outcomes and economic costs due to incorrect indication for resection. In the detection of liver metastases, contrast-enhanced MRI showed high sensitivity and specificity; however, the cost-effectiveness compared to the standard of care imaging remains unclear. The aim of this study was to analyze whether additional MRI of the liver is a cost-effective approach compared to routinely acquired contrast-enhanced computed tomography (CE-CT) in the initial staging of pancreatic cancer.MethodsA decision model based on Markov simulation was developed to estimate the quality-adjusted life-years (QALYs) and lifetime costs of the diagnostic modalities. Model input parameters were assessed based on evidence from recent literature. The willingness-to-pay (WTP) was set to $100,000/QALY. To evaluate model uncertainty, deterministic and probabilistic sensitivity analyses were performed.ResultsIn the base-case analysis, the model yielded a total cost of $185,597 and an effectiveness of 2.347 QALYs for CE-MR/CT and $187,601 and 2.337 QALYs for CE-CT respectively. With a net monetary benefit (NMB) of $49,133, CE-MR/CT is shown to be dominant over CE-CT with a NMB of $46,117. Deterministic and probabilistic survival analysis showed model robustness for varying input parameters.ConclusionBased on our results, combined CE-MR/CT can be regarded as a cost-effective imaging strategy for the staging of pancreatic cancer.Key Points• Additional MRI of the liver for initial staging of pancreatic cancer results in lower total costs and higher effectiveness.• The economic model showed high robustness for varying input parameters.

Use of a standardized reporting template: can we improve report quality in pancreatic and peri-ampullary malignancy?

Accurate pancreatic and periampullary cancer staging with resectability assessment is vital to optimize surgical management and improve patient outcomes. The aim of this study is to assess the usefulness of a standardized reporting template. Retrospective review of all surgically managed patients with pancreatic or periampullary malignancy between January 2018 and June 2019. Pre-operative CT imaging report was anonymised and audited against a modified NCCN reporting template. The same imaging studies were re-reported by two experienced GI radiologists using the same template. Fifty-nine patients (37 male) with median age of 68 years (36-83) underwent surgery for suspected pancreatic/peri-ampullary malignancy. The median time between pre-operative CT scan and surgery was 56.5 days (14-225). The use of reporting template resulted in significant increase in number of reported key features (p <0.005), interobserver agreed features (p< 0.005) and overall k-value assessed interobserver agreement (p< 0.005). Template reports correlated closely with key intraoperative findings whilst primary free text reports did not (k-value 0.85-0.96 versus 0.20-0.46, p< 0.05). The use of a reporting template resulted in a more complete and accurate pancreatic/peri-ampullary tumour evaluation, improved inter-observer relatability and correlation with intraoperative findings.

Characterization of the GATA Transcription Factor Family and Exploration of Their Relevance to Immune Infiltration and Tumor Microenvironment in Pancreatic Cancer.

BackgroundPancreatic cancer (PC) presents a phenomenal disease burden worldwide. The GATA transcription factor family is associated with a variety of human malignancies. However, the relation between GATA family members (GATAs) and PC has not been elucidated.MethodsThis study integrates large-scale bioinformatics database resources to analyze the expression patterns of GATAs in PC patients and explore their underlying function mechanism and relevance to immune infiltration and other different cell types in the tumor microenvironment in pancreatic cancer. First, the expression pattern of GATAs in pancreatic cancer was detected by the Oncomine database and the Gene Expression Profile Interaction Analysis (GEPIA2) database and verified through other datasets in the R2 platform. Then, we used the cBioPortal database and the Human Protein Atlas to assess the correlation between GATAs and clinicopathological features of PC. Then, survival analyses were performed to identify candidate prognostic factors in the GATA family in PC patients. Further, we performed gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) network, immune-infiltration correlation analysis, and cell type analysis of the tumor microenvironment at the single-cell level to explain the function of GATAs in pancreatic cancer.ResultsWe found that GATA3 and GATA6 were highly expressed in pancreatic cancer, and the expression levels of GATA4 and GATA6 correlated with the pathological stage, differentiation grade, and molecular subtype of pancreatic cancer. The survival analysis revealed that lower GATA4 of PC patients was associated with better outcomes, and higher GATA6 might be associated with longer OS. In addition, GATA3 was associated with immune cell infiltration of PC, and GATA6 was mainly distributed in the epithelial cells with ductal phenotype.ConclusionThis work tentatively identified GATA3, GATA4, and GATA6 in the GATA family associated with pancreatic cancer. GATA4 may serve as a prognostic factor for PC patients, and GATA6 may act as a subtype marker for PC. In addition, GATA3 may reflect the immune-infiltration status of PC.

Applications of PET/MRI in Abdominopelvic Oncology.

With PET/MRI, the strengths of PET and MRI are combined to allow simultaneous image acquisition and near-perfect image coregistration. MRI is increasingly being used for staging and restaging of abdominopelvic oncologic lesions, including prostate, hepatobiliary, pancreatic, neuroendocrine, cervical, and rectal cancers. Fluorine 18-fluorodeoxyglucose PET/CT has long been considered a cornerstone of oncologic imaging, and the development of multiple targeted radiotracers has led to increased research on and use of these agents in clinical practice. Thus, simultaneously performed PET/MRI enables the acquisition of complementary imaging information, with distinct advantages over PET/CT and MR image acquisitions. The authors provide an overview of PET/MRI, including descriptions of the major differences between PET/MRI and PET/CT, as well as case examples and treatment protocols for patients with commonly encountered malignancies in the abdomen and pelvis. Online supplemental material is available for this article. ©RSNA, 2021.

Combined inhibition of CXCL12 and PD-1 in MSS colorectal and pancreatic cancer: modulation of the microenvironment and clinical effects

BackgroundImmunotherapy in microsatellite stable colorectal or pancreatic cancer has not shown promising results. It has been hypothesized that targeting immunosuppressive molecules like SDF1-alpha/CXCL12 could contribute to immunotherapy and animal models...

Endoscopic Ultrasound-Guided Acquisition of Portal Venous Circulating Tumor Cells as a Potential Diagnostic and Prognostic Tool for Pancreatic Cancer.

BackgroundCirculating tumor cells (CTCs) were a promising liquid biopsy for pancreatic cancer (PC) but circulate in low counts in peripheral blood. We evaluated the diagnostic and prognostic values of portal vein (PoV) CTCs in PC patients.MethodsPoV was aspirated under EUS guidance from 40 patients with suspected pancreaticobiliary cancers. Epithelial–mesenchymal-transition-related subtypes of CTCs were identified via immunofluorescence using EpCAM and Twist antibodies. The diagnostic and prognostic performance of PoV CTCs was investigated by receiver-operating characteristic (AUC) curve and Kaplan–Meier survival analysis.ResultsIn total, 40 patients including 31 with PC, 4 with non-pancreatic periampullary cancer and 5 with benign pancreatic diseases (BPD) were enrolled. CTCs were detected more in PoV compared with peripheral blood. PoV CTC numbers in BPD patients were lower than in PC patients. The number of PoV CTCs, especially mesenchymal-CTCs (M-CTCs), was positively correlated with the tumor burden, instead of epithelial-CTCs (E-CTCs). The combination of PoV CTC numbers and CA19-9 demonstrated better diagnostic efficiency (AUC value 0.987) than either alone in differentiating PC with BPD. Moreover, the diagnostic efficacy of PoV CTCs and M-CTCs were obviously better than that of E-CTCs and CA19-9 in distinguishing early and late stage PC. Lastly, high PoV CTC and M-CTC numbers were both associated with shorter overall survival.ConclusionAcquisition of the PoV samples in PC patients via EUS-guided procedures has been proved safe and feasible. PoV CTCs, especially M-CTCs, have great potentials in diagnosing and predicting the prognosis of PC, especially in combination with CA19-9.

Utility of 18F-FDG PET/CT in Management of Pancreatic and Periampullary Masses-Prospective Study from a Tertiary Care Center.

Characterizing a pancreatic or periampullary mass lesion as benign or malignant on conventional imaging is difficult due to overlapping morphological features. 18F-FDG PET/CT is a molecular imaging technique with reportedly higher sensitivity and specificity in the differentiation of benign and malignant pancreatic and periampullary masses. In this prospective study, we evaluated the utility of 18F-FDG PET/CT in patients with recently diagnosed pancreatic and periampullary masses. Based on FDG uptake pattern, diffuse or absent uptake was considered benign and focal increased uptake as malignant. Among the 32 patients included in the study, pathological examination confirmed 25 as positive for malignancy and the remaining 7 as benign etiology. Based on FDG uptake pattern, sensitivity, specificity, PPV, NPV, and accuracy of the study were 92%, 42.8%, 85.2%, 60%, and 81.3% respectively. 18F-FDG PET/CT had a statistically significant higher detection rate in the evaluation of regional lymph nodes and distant organ metastases compared to radiological imaging. In 7/25 (14%) malignant cases, 18F-FDG PET/CT detected additional distant metastases which were not detected by conventional imaging and thus resulting in change in management from curative resection to palliative therapy. To conculde, 18F-FDG PET/CT uptake pattern can characterize pancreatic and periampullary masses as benign or malignant with a relatively good accuracy. Using 18F-FDG PET/CT for initial staging of pancreatic and periampullary cancer helps in appropriate staging and optimal selection of treatment modality compared to conventional imaging techniques.

Barriers and enablers to the implementation of multidisciplinary team meetings: a qualitative study using the theoretical domains framework

BackgroundEvidence-based clinical practice guidelines recommend discussion by a multidisciplinary team (MDT) to review and plan the management of patients for a variety of cancers. However, not all patients diagnosed with...

Improved Particle Swarm Optimization for Detection of Pancreatic Tumor using Split and Merge Algorithm

ABSTRACT Pancreatic cancer is the fourth leading cause of cancer-related death worldwide. Pancreatic tumours are characterised by a peculiar cell progression in intestinal enzymes and hormone-producing cells. Patients with pancreatic tumours have a shorter survival period depending on the type of tumour they have. Enhancing patient survival, diagnosing patients with malignant pancreatic tumours as soon as possible is the need of hour. The commonly used approach for diagnosis and clinical disease staging of pancreatic cancer is Computed Tomography (CT). However, because most abdominal CT images contain noise in addition to visceral fat in the vicinity of the pancreas, prompt detection is difficult, which requires an algorithm that distinguishes the anatomical structure clearly. This paper proposes, Particle Swarm Optimisation incorporating Split and Merge Segmentation to obtain enhanced CT images of pancreatic tumour. The image undergoes image processing procedures such as segmentation using PSO and fetch an enhanced output image with the help of gaussian filter. The algorithm outperforms Conventional PSO in terms of Entropy and Contrast, according to experimental results. The improved CT scans aid in the early detection and diagnosis of pancreatic cancer.

Graphene-Assisted Electrochemical Sensor for Detection of Pancreatic Cancer Markers.

Pancreatic cancer is a highly lethal gastrointestinal malignancy. Most patients are already in the middle to advanced stages of pancreatic cancer at the time of diagnosis and cannot be treated completely. As a single-atom planar two-dimensional crystal, graphene’s unusual electronic structure, specific electronic properties and excellent electron transport capacity make it uniquely advantageous in the field of electrochemical sensing. In this mini-review, we summarize the potential application of graphene in pancreatic cancer detection. K-Ras gene, CEA and MicroRNA are important in the early diagnosis of pancreatic cancer.

Refined prognostic staging for resected pancreatic cancer by modified stage grouping and addition of tumour grade

BackgroundWith changes in T and N categories the 8th edition of the AJCC/UICC TNM staging system for pancreatic cancer resulted in improved prognostic staging, but inconsistencies were observed with specific stage groups. Tumour grading remains disregarded in prognostic staging. We aimed to validate the current staging system and to investigate the possibility of further optimization by integration of grading. Methods1946 patients undergoing upfront surgical resection for pancreatic adenocarcinoma from 10/2001 to 12/2015 were identified from a prospective institutional database. Survival analyses based on the 8th UICC TNM edition were performed and rare TNM subgroups were reallocated based on survival. The impact of tumour grade on stage-specific survival was assessed and a TNMG staging system was developed. ResultsThe 8th UICC staging system accurately stratified prognosis except for comparable survival in stages IB (pT2N0M0) and IIA (pT3N0M0). Regrouping of pT3N0M0 and pT1N1M0 to IB and of pT1N2M0 to II resulted in a modified staging system with higher consistency. High tumour grade (G3&G4 vs G1&G2) was associated with a significantly shorter survival in all new stage groups except for stage IV modified UICC. A TNMG-based prognostic stage grouping in which high tumour grade results in grouping with tumours of the next higher pTNM-stage resulted in improvement of prognostication in non-metastatic pancreatic cancer. ConclusionsThe 8th edition of the UICC TNM staging system leaves room for improvement. A TNMG staging system with adjustments in group-allocation of specific rarely occurring pTNM subgroups and integration of tumour grade results in improved prognostic stratification.

Cost evaluation of an exercise oncology intervention: The exercise in all chemotherapy trial.

BackgroundThere is strong evidence supporting the efficacy of exercise oncology programs to improve physical and psychosocial outcomes during active treatment. However, there is a paucity of evidence on the effect of exercise on healthcare utilization and cost analyzes of exercise oncology programs.AimsOur objective was to assess the effects of a pragmatic exercise oncology program (ENACT) during active chemotherapy treatment on healthcare utilization and associated costs.MethodsWe conducted post‐hoc analyzes on 160 ENACT participants and 75 comparison participants matched on cancer site, stage, age range, and gender. We obtained complete healthcare utilization histories for each patient (specific to emergency department [ED] visits and hospital admissions) coinciding with their participation in ENACT. A sub‐analysis was conducted for advanced stage breast, gastrointestinal, and pancreatic cancer patients.ResultsHealthcare costs for patients who participated in the ENACT exercise oncology intervention were numerically lower than healthcare costs for the comparison group, even after accounting for the cost of the intervention. However, the differences were not statistically significant.ConclusionOur findings suggest that an exercise oncology program during active chemotherapy treatment are at least cost neutral for all cancer patients, including advanced stage cancers. Additional research is warranted to evaluate the potential for exercise oncology programs to reduce healthcare utilization, particularly in advanced cancer patients.

The role of radiotherapy for pancreatic malignancies: a population-based analysis of the SEER database

BackgroundTo investigate the role of adjuvant radiotherapy in patients with pancreatic cancer.Methods and patientsThe patients with pancreatic cancer from 18 registered institutions in the Surveillance Epidemiology and End Results (SEER) database were retrospectively analyzed. The characteristics of patients who would benefit from adjuvant radiotherapy were screened, as well as whether neoadjuvant or adjuvant radiotherapy conferred to a better clinical outcome. Propensity score matching was used to control for confounding features.ResultsThirty thousand two hundred and forty-nine patients were included in this study (21,295 vs 8954 in surgery and adjuvant radiotherapy group); 1150 patients were matched in two groups. The median survivals in the surgery (S) group and adjuvant radiotherapy (S + R) group were 24 and 21 months, respectively. The 1-, 3-, and 5-year overall survival (OS) rates in the S group and S + R group were 68%, 40%, 31%, and 75%, 30%, 20%, respectively (p < 0.001), and the median OS was 22 and 25 months in S and S + R group after PSM, the former 1-, 2-, 3-, and 5-year OS were 73%, 45%, 30%, and 19%, and the later were 81%, 52%, 37%, and 24% (p = 0.0015), respectively; stratified analysis showed patients whose carcinoma located at pancreatic head with II stage infiltrating duct carcinoma (22 vs 25, p = 0.0276), T4 adenocarcinoma (28 vs 33, p = 0.0022), N1 stage adenocarcinoma (20 vs 23, p = 0.0203), and patients with infiltrating duct carcinoma received regional resection (23 vs 25, p = 0.028) and number of resected lymph node were ≥ 4 (22 vs 25, p = 0.009) had better OS after additional radiotherapy than surgery alone. Patients with pancreatic body/tail carcinoma III stage adenocarcinoma (13 vs, p = 0.0503) and T4 adenocarcinoma (14 vs, p = 0.0869) had survival advantage within 24 months for additional radiotherapy. However, patients with T2 stage adenocarcinoma located in pancreatic body/tail had better OS in surgery group than that in R + S group.ConclusionsAdditional radiotherapy may contribute to improved prognosis for patients with pancreatic head II stage infiltrating duct carcinoma, III stage adenocarcinoma, T4 stage carcinoma, N1 stage adenocarcinoma, regional resection, or number of lymphadenectomy ≥ 4 in infiltrating duct carcinoma. A specific subgroup of patients with specific stage and histological type pancreatic cancer should be considered for additional radiotherapy.

Abstract 478: Extracellular vesicle based multi-omics prediction model for the early detection of pancreatic cancer

Abstract Introduction: Pancreas cancer (PC) is projected to become the third leading cause of cancer deaths in the US, however there is no screening test in routine clinical use. A minimally invasive test for early detection of PC is a critical unmet clinical need. Extracellular vesicles (EVs) shed into the circulation include a diverse array of surface and cargo biomolecules that can be leveraged as biomarkers for the early detection of PC. We hypothesize that systemic molecular characterization of plasma EVs, secreted by latent yet progressing precursor lesions (PL) of the pancreas, may lead to the development of high accuracy classification algorithms for stratification of patients for the early detection of PC. Herein, we developed a liquid biopsy-based PACE assay (Pancreatic Cancer Exosomics) comprised of a multi-omics (proteomics, metabolomics, and lipidomics) biomarker panel. Methods: To develop a functional EV-based multi-omics biomarker panel, we performed metabolomics, lipidomics and proteomics analysis of EVs from high quality pre-surgery, fasting plasma samples obtained from patients with early stage pancreatic cancer (IA, IB and IIA) (N= 60), normal control subjects without cancer (N = 50), patients diagnosed with pancreatitis (benign) (N= 39), and early stage colorectal cancer (N=30) as related disease cohorts. For selection of candidate biomarkers, we randomly divided 3/5th of the sample set as discovery and the remainder 2/5th as the test cohort. To consider the effect of potential correlation for predictors, we applied the elastic net penalty to generalized linear model (ELNET). A 100-fold cross-validation approach was used to determine tuning parameters and calibrate the prediction model in the discovery set. Results: These analyses allowed us to develop a 12 analyte multi-omics panel that could discriminate early stage PC from normal controls (NC) with 98.2% accuracy (Specificity (SP) = 85.2% and Sensitivity (SN) = 71.5%) and 95.4% accuracy (SP = 92.8% and SN = 59.3%) for discovery and validation sets, respectively. A unique aspect of the study design was the inclusion of control cohorts to eliminate non-specific markers. Furthermore, extensive clinical outcome data allowed us to develop multi-analyte predictors of overall survival and progression free survival with high accuracy. Validation of these findings using orthogonal methods is ongoing. Conclusions: In summary, these preliminary data provide strong support for the development of a liquid biopsy-based EV biomarker panel for the early detection of PC. We believe the positive predictive value (PPV) of this panel can be further improved in conjunction with serum CA 19-9 that is in routine clinical use. Citation Format: Yaoxiang Li, Keith Unger, Charles Hinzman, Meth Jayatilake, Anton Iliuk, Shivani Bansal, Michael Girgis, Partha Banerjee, John B. Tyburski, Todd Bauer, Amrita K. Cheema. Extracellular vesicle based multi-omics prediction model for the early detection of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 478.

Abstract 17: Proteogenomic characterization of pancreatic ductal adenocarcinoma

Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive cancer with 5-year survival rate less than 10%. Although numerous efforts have been made to characterize the functional driver genes of PDAC, the impacts of genomic alterations on protein modifications and molecular mechanism of this cancer type are still not well defined. To this end, Investigators from The Clinical Proteomic Tumor Analysis Consortium (CPTAC) conducted the first comprehensive characterization of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues using whole genome sequencing, whole exome sequencing, methylation, RNA-seq, miRNA-seq, proteomics, phosphoproteomics, and glycoproteomics. To address the inherent low neoplastic cellularity of pancreatic cancer, multiple orthogonal strategies using molecular features and histology imaging were deployed to deconvolute the cellularity and identify 105 tumors with sufficient neoplastic purity for downstream analyses. Proteomics, phosphoproteomics, and glycoproteomics analyses by mass spectrometry identified and quantified 11,662 proteins, 51,469 phosphosites, and 34,024 glycopeptides, respectively. Genomic data revealed that 97% of the cancers harbored KRAS alterations in our cohort. In addition, we found that somatic mutations and copy number alterations could impact gene and protein expression, as well as protein modifications such as phosphorylation and glycosylation. Glycoproteomic analyses uncovered tumor-associated alterations in glycoprotein biosynthesis and glycoproteins as potential targets for diagnosis or therapeutic intervention. Over-expressed kinase substrates and their corresponding kinases were identified with integration of global proteomic and phosphoproteomic measurements, thus identifying potential therapeutic targets. The results of our molecular and cellular subtyping revealed a small group of immune-hot subtype tumors that could benefit from immunotherapy, as well as the underlying mechanisms associated with major groups of immune-cold subtypes, including endothelial cell remodeling, glycolysis, and cell junction dysregulation. Non-negative matrix factorization (NMF)-based proteogenomics subtyping revealed two clusters with strong prognostic relevance. Finally, we identified proteins and glycoproteins overexpressed in early stage pancreatic cancer that may serve as candidates for early detection. This comprehensive proteogenomic characterization of PDAC provides a valuable resource for uncovering the molecular mechanisms of this cancer and thus paves the way for discovery of novel early detection and therapeutic targets. Citation Format: Liwei Cao, Chen Huang, Daniel Cui Zhou, Oliver F. Bathe, Daniel W. Chan, Ralph H. Hruban, Li Ding, Bing Zhang, Hui Zhang, Clinical Proteomic Tumor Analysis Consortium Investigators. Proteogenomic characterization of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 17.

How many number of retrieved lymph nodes is required for accurate N-staging in resected pancreatic cancer?

Although N stage is important factor in survival of resected pancreatic cancer, appropriate number of retrieved lymph nodes for accurate staging is still controversial. From 1993 to 2019, 446 patients underwent pancreatectomy for pancreatic cancer were included. The binomial probability law was applied to define the minimum number of examined LNs (minELN). The prognostic factors for overall survival were analyzed. According to binomial probability law, 12 and 20 retrieved lymph nodes were found to be required accurate staging for pancreatic cancer. With node-positive disease, the median OS of patients with less than 12 ELNs was not significantly different to those with 12 or more ELNs (20 v. 18 months, p = 0.326). However, N stage determination (N1 v. N2) was accurate in stratifying oncologic outcomes even when finding fewer than 12 ELNs (26 v. 19 months, p = 0.04) and more than 12 ELNs (22 v. 18 months, p = 0.01). On the other hand, with node-positive disease, the median OS of patients with less than 20 ELNs was not significantly different to those with 20 or more ELNs (20 v. 20 months, p = 0.78). However, N stage determination (N1 v. N2) was accurate in stratifying oncologic outcomes in fewer than 20 ELNs (23 v. 17 months, p = 0.015), but SHOWED no significant IN MORE THAN 20 ELNs (22 v. 18 months, p = 0.07). AJCC (8TH) N-staging system in independent prognostic factor for long-term survival of resected pancreatic cancer.Retrieving 12 lymph nodes are appropriate for Nodal staging PDAC by using AJCC (8th) N stage.