Staging Of Pancreatic Adenocarcinoma Research Articles

A mathematical model for pancreatic cancer during intraepithelial neoplasia.

Cancer is the result of complex interactions of intrinsic and extrinsic cell processes, which promote sustained proliferation, resistance to apoptosis, reprogramming and reorganization. The evolution of any type of cancer emerges from the role of the microenvironmental conditions and their impact of some molecular complexes on certain signalling pathways. The understanding of the early onset of cancer requires a multiscale analysis of the cellular microenvironment. In this paper, we analyse a qualitative multiscale model of pancreatic adenocarcinoma by modelling the cellular microenvironment through elastic cell interactions and their intercellular communication mechanisms, such as growth factors and cytokines. We focus on the low-grade dysplasia (PanIN 1) and moderate dysplasia (PanIN 2) stages of pancreatic adenocarcinoma. To this end, we propose a gene-regulatory network associated with the processes of proliferation and apoptosis of pancreatic cells and its kinetics in terms of delayed differential equations to mimic cell development. Likewise, we couple the cell cycle with the spatial distribution of cells and the transport of growth factors to show that the adenocarcinoma evolution is triggered by inflammatory processes. We show that the oncogene RAS may be an important target for developing anti-inflammatory strategies that limit the emergence of more aggressive adenocarcinomas.

Quantitative Edge Analysis Can Differentiate Pancreatic Carcinoma from Normal Pancreatic Parenchyma.

This study aimed to introduce specific image feature analysis, focusing on pancreatic margins, and to provide a quantitative measure of edge irregularity, evidencing correlations with the presence/absence of pancreatic adenocarcinoma. We selected 50 patients (36 men, 14 women; mean age 63.7 years) who underwent Multi-detector computed tomography (MDCT) for the staging of pancreatic adenocarcinoma of the tail of the pancreas. Computer-assisted quantitative edge analysis was performed on the border fragments in MDCT images of neoplastic and healthy glandular parenchyma, from which we obtained the root mean square deviation SD of the actual border from the average boundary line. The SD values relative to healthy and neoplastic borders were compared using a paired t-test. A significant SD difference was observed between healthy and neoplastic borders. A threshold SD value was also found, enabling the differentiation of adenocarcinoma with 96% specificity and sensitivity. We introduced a quantitative measure of boundary irregularity, which correlates with the presence/absence of pancreatic adenocarcinoma. Quantitative edge analysis can be promptly performed on select border fragments in MDCT images, providing a useful supporting tool for diagnostics and a possible starting point for machine learning recognition based on lower-dimensional feature space.

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.

Clinical application of Al18F-NOTA-FAPI PET/CT in diagnosis and TNM staging of pancreatic adenocarcinoma, compared to 18F-FDG

PurposeThis study aimed to investigate the ability of Al18F-NOTA-FAPI PET/CT to diagnose pancreatic carcinoma and tumor-associated inflammation with the comparison of 18F-FDG PET/CT.MethodsProspective analysis of Al18F-NOTA-FAPI PET/CT and 18F-FDG PET/CT scans of 31 patients from 05/2021 to 05/2022 were analyzed. Al18F-NOTA-FAPI imaging was performed in patients who had Ce-CT and FDG PET/CT and the diagnosis was still unclear. Follow-up histopathology or radiographic examination confirmed the findings. Radiotracer uptake, diagnostic performance, and TNM (tumor-node-metastasis) classifications were compared.ResultsA total of 31 patients with pancreatic carcinoma (all were adenocarcinoma) underwent Al18F-NOTA-FAPI-04 PET/CT, including 20 male and 11 female patients, with a mean age of 58.2 ± 8.5 years. FAPI-04 PET/CT imaging showed a higher value of SUVmax-15min/30min/60min, SUVmean-15min/30min/60min, TBR1, and TBR2 in pancreatic carcinoma than FDG (all P < 0.01). The mean level of Al18F-NOTA FAPI-04 uptake values of the pancreatic ductal adenocarcinoma was higher than that of pancreatitis in both SUVmax-30min (P < 0.01), SUVmean-30min (P < 0.05), SUVmax-60min (P < 0.01), and SUVmean-60min (P < 0.01). The FAPI △SUVmax-1, △SUVmax-2, and △SUVmean-2 uptake values of pancreatic carcinoma were higher than tumor-associated inflammation (all P < 0.01). TNM staging of 16/31 patients changed after Al18F-NOTA FAPI-04 PET/CT examination with all upstaging changes.ConclusionAl18F-NOTA-FAPI-04 PET/CT at 15 and 30 min also demonstrated an equivalent detection ability of pancreatic lesion to 18F-FDG PET/CT. Delayed-phase Al18F-NOTA-FAPI-04 PET/CT can help differentiate pancreatic carcinoma and tumor-associated inflammation. Al18F-NOTA FAPI-04 PET/CT also performed better than FDG PET/CT in TNM staging.Trial registrationChinese Clinical Trial Registry, ChiCTR2100051406. Registered 23 September 2021, https://www.chictr.org.cn/showproj.html?proj=133033

ASO Visual Abstract: The Impact of Medicaid Expansion on Early Stage Pancreatic Adenocarcinoma at High- versus Low-Volume Facilities.

ASO Visual Abstract: The Impact of Medicaid Expansion on Early Stage Pancreatic Adenocarcinoma at High- versus Low-Volume Facilities.

Maintaining early diagnosis of pancreatic adenocarcinoma in Japan: Local resilience against COVID-19

Background and aimsThis study evaluated the impact of the coronavirus disease 2019 (COVID-19) pandemic on pancreatic adenocarcinoma (PA) practice in our region and discussed the effects of our institution's regional collaborative system, the “Early Stage Pancreatic Cancer Diagnosis Project," which was originally unrelated to this study's purpose. MethodsWe retrospectively investigated 150 patients with PA at Yokohama Rosai Hospital by defining three time periods: before (C0), during the first year (C1), and during the second year (C2) of the COVID-19 pandemic. ResultsAmong the three periods (C0, C1, and C2), there were significantly less patients with stage I PA (14.0%, 0%, and 7.4%, p = 0.032) in C1, and significantly more patients with stage III PA (10.0%, 28.3%, and 9.3%, p = 0.014) in C1. The pandemic significantly prolonged the median durations from disease onset to patients’ first visits (28, 49, and 14 days, p = 0.012). In contrast, there was no significant difference in the median durations from referral to first visit to our institution (4, 4, and 6 days, p = 0.391). ConclusionsThe pandemic advanced the stage of PA in our region. Although the pancreatic referral network remained functional during the pandemic, there were delays from disease onset to patients' first visit to healthcare providers, including clinics. While the pandemic caused temporary damage to PA practice, the routine regional collaboration provided by our institution's project allowed for early resilience. A notable limitation is that the impact of the pandemic on PA prognosis was not evaluated.

A retrospective preliminary study of intrapancreatic late enhancement as a noteworthy imaging finding in the early stages of pancreatic adenocarcinoma.

To characterize intrapancreatic late enhancement (ILE) observed in the early stages of pancreatic adenocarcinoma (PAC). Among 203 patients pathologically diagnosed with PAC between October 2011 and February 2021, 32 patients with pre-diagnostic abdominal contrast-enhanced CT performed from 6months to 5years before the diagnosis were enrolled in this study. Indirect findings (IFs) on pre-diagnostic CT, including ILE, were evaluated and examined for various clinical data and time intervals to diagnosis (TIDs). The detected ILE was quantitatively evaluated, and the effect of ILE awareness on lesion detection by two radiologists and their interobserver agreement were assessed. Among the 32 patients, 23 showed IFs. ILE was observed in 14 patients (63%), with a median TID of 17months (interquartile ratio [IQR]: 9.3-42.3). ILE alone was observed in eight patients (35%), ILE with focal pancreatic parenchymal atrophy (FPPA) was observed in five patients (22%), and ILE with main pancreatic duct abnormalities (MPDA) was observed in one patient (4%). Pancreatic head lesions were significantly more frequent in patients with ILE alone than in patients with FPPA or MPDA (p = 0.026). The median long-axis diameters of the region with ILE and ILE-to-pancreas contrast were 10 (IQR: 5-11) mm and 24 (IQR: 17-33) HU, respectively. Awareness of ILE led observers to detect two or three more pancreatic head lesions, and interobserver agreement increased from poor agreement (k = 0.17) to moderate agreement (k = 0.55). ILE is a significant IF for early PAC detection. • Intrapancreatic late enhancement (ILE) is a significant indirect finding in the early detection of pancreatic adenocarcinoma. • ILE without other indirect findings is expected to help detect pancreatic head lesions. • Image evaluation focusing on ILE can increase lesion detection and improve the interobserver agreement.

An analysis on the effect of income change in the resection of early stage pancreatic adenocarcinoma

An analysis on the effect of income change in the resection of early stage pancreatic adenocarcinoma

Expression, oncological and immunological characterizations of BZW1/2 in pancreatic adenocarcinoma.

Background: Despite the progress in early diagnosis and treatment, prognosis of pancreatic adenocarcinoma (PAAD) is still poor. Basic leucine zipper and W2 domain-containing protein 1 (BZW1) and protein 2 (BZW2) are attached to the basic leucine zipper (bZIP) superfamily. Recently, BZW1 was identified as an important role in glycolysis of PAAD. However, the comprehensive reports about BZW1/2 in PAAD are not sufficient. Methods: RNA-seq data in the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were retrospectively analyzed. We explored the expression of BZW1/2 in PAAD tissues and the associations between BZW1/2 and prognosis. In addition, the potential roles of BZW1/2 in tumor microenvironment (TME) of PAAD were analyzed. Finally, clinicopathological data of 49 patients with PAAD in our institution were collected. Immunohistochemistry was used to determine the expression of BZW1/2 in PAAD samples. Results: BZW1 and BZW2 were upregulated in PAAD tissues compared to normal tissues (p < 0.05). The expression of BZW1/2 were not significantly correlated with gender, grade and stage of PAAD (p > 0.05). High expression of BZW2 was an independent predictor for poor prognosis of PAAD (HR 1.834, 95%CI 1.303–2.581, p = 0.001). And a nomogram to predict overall survival (OS) of PAAD was established with a C-index of 0.685. BZW1 and BZW2 expression were positively associated with T cell mediated immune response to tumor cell and Th2 cells in xCell database. Tumor Immune Single-Cell Hub (TISCH) analyses indicated that BZW1 and BZW2 were mainly expressed in B cells and malignant cells. External cohort furtherly validated that high expression of BZW1 and BZW2 were predictors for poor prognosis of PAAD. Conclusion: We found that BZW1 and BZW2 are highly expressed in malignant cells and B cells in the TME of PAAD. BZW2 is an independent predictor for OS of PAAD. BZW1 and BZW2 expression are positively associated with T cell mediated immune response to tumor cell and Th2 cells in PAAD.

Evolving management of early stage pancreatic adenocarcinoma in older patients

BackgroundDue to the aging population, the number of older patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) will continue to rise. Study designUtilizing the NCDB from 2010 to 2016, patients with early stage, clinically node negative PDAC who were ≥70 years old and had a Whipple were identified. Multivariable logistic regressions were used to determine independent factors for R0 resection and NAT. Cox-proportional-hazards regression analyses examined for the impact of NAT on the risk of death. ResultsOf 5086 patients, 51.7% received upfront surgery + adjuvant therapy (UFS + AT), followed by 29.9% UFS only, and the remainder NAT. NAT significantly improved OS compared to a combined cohort of those that had UFS ± AT. NAT retained its independent survival benefit when compared to only patients that had UFS + AT. ConclusionFor older patients diagnosed with early stage PDAC, NAT was associated with improved R0 resection rates and a significant survival benefit when compared to the current standard of care.

Genetic polymorphisms and their influence on pancreatic adenocarcinoma progression

Pancreatic adenocarcinoma (PA) is one of the most fatal cancers since it shows little to no symptoms until it has metastasized. As is true with most malignancies, an early detection and diagnosis is imperative in order to help increase survival rate. Although there are several extant treatments available, their success depends on an early diagnosis. In order to identify genetic loci that may assist in early diagnosis, we analyzed 134 DNA sequences of patients with various stages of PA. NCBI’s Gene Expression Omnibus was used to obtain PA microarray data to identify overexpressed genes. The Sequence Read Archive (SRA) database was then used to provide sequenced data of a PA cohort which was then mapped, indexed and called. With these analyses, we were able to identify single nucleotide polymorphisms (SNPs) that were specific to PA primary, secondary, or metastatic tumors. These results advance our understanding of the development of PA and highlight target sites that could influence PA tumor stages.

Structured Reporting of Computed Tomography and Magnetic Resonance in the Staging of Pancreatic Adenocarcinoma: A Delphi Consensus Proposal.

Background: Structured reporting (SR) in radiology has been recognized recently by major scientific societies. This study aims to build structured computed tomography (CT) and magnetic resonance (MR)-based reports in pancreatic adenocarcinoma during the staging phase in order to improve communication between the radiologist and members of multidisciplinary teams. Materials and Methods: A panel of expert radiologists, members of the Italian Society of Medical and Interventional Radiology, was established. A modified Delphi process was used to develop the CT-SR and MRI-SR, assessing a level of agreement for all report sections. Cronbach’s alpha (Cα) correlation coefficient was used to assess internal consistency for each section and to measure quality analysis according to the average inter-item correlation. Results: The final CT-SR version was built by including n = 16 items in the “Patient Clinical Data” section, n = 11 items in the “Clinical Evaluation” section, n = 7 items in the “Imaging Protocol” section, and n = 18 items in the “Report” section. Overall, 52 items were included in the final version of the CT-SR. The final MRI-SR version was built by including n = 16 items in the “Patient Clinical Data” section, n = 11 items in the “Clinical Evaluation” section, n = 8 items in the “Imaging Protocol” section, and n = 14 items in the “Report” section. Overall, 49 items were included in the final version of the MRI-SR. In the first round for CT-SR, all sections received more than a good rating. The overall mean score of the experts was 4.85. The Cα correlation coefficient was 0.85. In the second round, the overall mean score of the experts was 4.87, and the Cα correlation coefficient was 0.94. In the first round, for MRI-SR, all sections received more than a good rating. The overall mean score of the experts was 4.73. The Cα correlation coefficient was 0.82. In the second round, the overall mean score of the experts was 4.91, and the Cα correlation coefficient was 0.93. Conclusions: The CT-SR and MRI-SR are based on a multi-round consensus-building Delphi exercise derived from the multidisciplinary agreement of expert radiologists in order to obtain more appropriate communication tools for referring physicians.

Case series: FDG-avid lymphadenopathy during oncologic staging of pancreatic adenocarcinoma after COVID-19 vaccination

: COVID-19 vaccination is becoming widely available to millions of patients across the world. Lymphadenopathy after recent COVID-19 vaccination is a common side effect that can cause upstaging in oncology patients as it can be misdiagnosed as metastatic disease. This can potentially change treatment and have devastating consequences. We present three cases of FDG-avid lymphadenopathy after recent COVID-19 vaccination in patients undergoing oncologic staging for pancreatic adenocarcinoma. Patient 1 is a 57-year-old female that developed FDG-avid supraclavicular lymphadenopathy after recent COVID-19 vaccination while undergoing pancreatic adenocarcinoma restaging. Excisional biopsy ruled out metastatic disease, and the patient subsequently underwent radiotherapy and surgery. Patients 2 and 3 are a 49-year-old female and 62-year-old male with pancreatic adenocarcinoma undergoing restaging that developed axillary FDG-avid lymphadenopathy after recent vaccination, respectively. The decision was made to observe the lymphadenopathy in both cases as they continued neoadjuvant chemotherapy since they were not metabolically optimized for surgery. Lymphadenopathy in oncology patients after recent COVID-19 vaccination should be managed with a multi-disciplinary team that includes the surgeon, oncologist, primary care provider, and radiologist. Factors such as surgical candidacy, likelihood of reactive lymphadenopathy, probability of metastatic disease, and risk of delaying surgery or treatment should be taken into consideration. Diagnostic imaging and procedures should be avoided if the outcome will not change treatment.

Role of 3D Volumetric and Perfusion Imaging for Detecting Early Changes in Pancreatic Adenocarcinoma.

PurposeThere is a major shortage of reliable early detection methods for pancreatic cancer in high-risk groups. The focus of this preliminary study was to use Time Intensity-Density Curve (TIDC) and Marley Equation analyses, in conjunction with 3D volumetric and perfusion imaging to demonstrate their potential as imaging biomarkers to assist in the early detection of Pancreatic Ductal Adenocarcinoma (PDAC).Experimental DesignsA quantitative retrospective and prospective study was done by analyzing multi-phase Computed Tomography (CT) images of 28 patients undergoing treatment at different stages of pancreatic adenocarcinoma using advanced 3D imaging software to identify the perfusion and radio density of tumors.ResultsTIDC and the Marley Equation proved useful in quantifying tumor aggressiveness. Perfusion delays in the venous phase can be linked to Vascular Endothelial Growth Factor (VEGF)-related activity which represents the active part of the tumor. 3D volume analysis of the multiphase CT scan of the patient showed clear changes in arterial and venous perfusion indicating the aggressive state of the tumor.ConclusionTIDC and 3D volumetric analysis can play a significant role in defining the response of the tumor to treatment and identifying early-stage aggressiveness.

Identification of the Real Hub Gene and Construction of a Novel Prognostic Signature for Pancreatic Adenocarcinoma Based on the Weighted Gene Co-expression Network Analysis and Least Absolute Shrinkage and Selection Operator Algorithms.

Background: Pancreatic adenocarcinoma (PAAD) has a considerably bad prognosis, and its pathophysiologic mechanism remains unclear. Thus, we aimed to identify real hub genes to better explore the pathophysiology of PAAD and construct a prognostic panel to better predict the prognosis of PAAD using the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithms.Methods: WGCNA identified the modules most closely related to the PAAD stage and grade based on the Gene Expression Omnibus. The module genes significantly associated with PAAD progression and prognosis were considered as the real hub genes. Eligible genes in the most significant module were selected for construction and validation of a multigene prognostic signature based on the LASSO-Cox regression analysis in The Cancer Genome Atlas and the International Cancer Genome Consortium databases, respectively.Results: The brown module identified by WGCNA was most closely associated with the clinical characteristics of PAAD. Scaffold attachment factor B (SAFB) was significantly associated with PAAD progression and prognosis, and was identified as the real hub gene of PAAD. Moreover, both transcriptional and translational levels of SAFB were significantly lower in PAAD tissues compared with normal pancreatic tissues. In addition, a novel multigene-independent prognostic signature consisting of SAFB, SP1, and SERTAD3 was identified and verified. The predictive accuracy of our signature was superior to that of previous studies, especially for predicting 3- and 5-year survival probabilities. Furthermore, a prognostic nomogram based on independent prognostic variables was developed and validated using calibration curves. The predictive ability of this nomogram was also superior to the well-established AJCC stage and histological grade. The potential mechanisms of different prognoses between the high- and low-risk subgroups were also investigated using functional enrichment analysis, GSEA, ssGSEA, immune checkpoint analysis, and mutation profile analysis.Conclusion: SAFB was identified as the real hub gene of PAAD. A novel multigene-independent prognostic signature was successfully identified and validated to better predict PAAD prognosis. An accurate nomogram was also developed and verified to aid in the accurate treatment of tumors, as well as in early intervention.

An Integrin-αvβ6/α5β1-Bitargeted Probe for the SPECT Imaging of Pancreatic Adenocarcinoma in Preclinical and Primary Clinical Studies.

Pancreatic adenocarcinoma (PA) is one of the deadliest human malignancies. However, early detection, prediction of surgical resectability, and prognosis of PA are challenging with current conventional imaging technologies in the clinic. Molecular imaging technologies combined with novel imaging probes could be useful for early detection and accurate staging of PA. Integrin αvβ6 and α5β1 are found to be overexpressed in PA. In this study, integrin αvβ6/α5β1-bitargeted probes 99mTc-HYNIC-isoDGR (99mTc-isoDGR) and 99mTc-HYNIC-PEG4-PisoDGR2 (99mTc-3PisoDGR2) were prepared and evaluated in the BxPC-3 human pancreatic tumor model. Both subcutaneous and in situ BxPC-3 tumors could be clearly visualized by 99mTc-isoDGR nanoScan SPECT/CT imaging with a high ratio of tumor to background. The blocking study with excess nonradioactive peptide showed a significantly reduced tumor uptake, which confirmed the specificity of 99mTc-isoDGR. Biodistribution results confirmed the imaging results. The dimer tracer 99mTc-3PisoDGR2 significantly enhanced tumor uptake compared with 99mTc-isoDGR, and the spontaneous PA lesion in the mouse model could be clearly visualized by 99mTc-3PisoDGR2. The primary clinical study also verified the ability of 99mTc-3PisoDGR2 for detection of PA. Therefore, SPECT/CT imaging using the integrin αvβ6/α5β1-bitargeted 99mTc-3PisoDGR2 provided a potential approach for the noninvasive detection of PA.

Predicting positive peritoneal cytology in pancreatic cancer.

Positive cytology from peritoneal washings obtained prior to potential resection of pancreatic cancer is associated with grim prognosis, equivalent to M1 disease. We examine our experience with pancreatic cancer patients who underwent pre-resection lavage in an attempt to predict who would have malignant cells on peritoneal cytology. We conducted a retrospective review of patients undergoing pancreatectomy for pancreatic adenocarcinoma at a tertiary care institution from 1995 to 2019 and had pre-resection lavage performed. Demographic and clinicopathologic data were collected. Logistic regression models were used to identify predictors of positive cytology. Three hundred ninety-nine patients underwent pancreatic resection and had lavage performed. Forty-three (10.8%) had positive peritoneal cytology. Those with positive cytology had higher median Ca19-9 value than those with negative cytology at diagnosis (368.5 vs 200 U/mL, p = 0.007) and after neoadjuvant therapy (100.3 vs 43 U/mL, p = 0.013). After controlling for preoperative therapy received, an initial Ca19-9 greater than 1220 U/mL (OR 2.72, 95% CI 1.07-6.89, p = 0.035), locally advanced disease (OR 4.86, 95% CI 1.31-18.09, p = 0.018), and BMI ≥ 25kg/m2 (OR 2.67, 95% CI 1.04-6.97, p = 0.042) were associated with positive cytology in multivariate logistic regression model. The associated ROC curve had an AUC of 0.7507, suggesting adequate discrimination of those with positive peritoneal cytology. Diagnostic laparoscopy remains an important adjunct to the workup, diagnosis, and staging of pancreatic adenocarcinoma. Patients with locally advanced disease, significantly elevated serum Ca19-9 at diagnosis, and BMI ≥ 25kg/m2 may be at higher risk for positive peritoneal cytology, regardless of whether neoadjuvant therapy is administered.

Neoadjuvant chemotherapy improves outcomes in resectable pancreatic adenocarcinoma: an updated national cancer database analysis

Presenter: Wade Christopher MD | Providence Saint John's Cancer Institute Background: Systemic chemotherapy has been shown to have a survival benefit for all stages of pancreatic adenocarcinoma. Historically adjuvant chemotherapy (AC) was given for all patients. However, recently there has been a shift towards neoadjuvant chemotherapy (NAC) for both resectable and borderline resectable pancreatic adenocarcinoma. This shift has been driven by the observation that many post-operative patients are unable to undergo treatment with AC secondary to surgical complications. The objective of this study was to compare survival and oncologic outcomes of NAC versus AC for early stage resectable pancreatic cancer. Methods: Patients age 18 years and older with stage I or II pancreatic adenocarcinoma in the 2010-2017 National Cancer Database were identified. Patients were grouped as receiving NAC + surgery compared to those patients who underwent upfront surgery +/- AC. Logistic regression evaluated the oncologic outcomes of positive resection margins and positive lymph nodes after NAC. Kaplan-Meier method followed by Cox proportional-hazards regression with inverse probability weighting (IPTW) using propensity score matching was used to compare overall survival (OS). Results: In 19,415 patients with early stage pancreatic adenocarcinoma who underwent surgery, upfront NAC led to a 13% risk reduction of a positive resection margin when compared to surgery +/- AC (odds ratio [OR]:0.87; 95%CI 0.78-0.97), and a 59% decreased risk of positive lymph nodes at the time of surgery (OR:0.41; 95%CI 0.38-0.45), after controlling for patient clinical and pathological risk factors. The median overall survival for all patients treated with NAC was 2.56 years versus 1.95 years for surgery +/- AC (3 and 5 year OS for NAC patients was 43.14% and 26.44%; 3 and 5 year OS for surgery +/- AC patients was 34.94% and 22.42%) (Log-rank p-value < 0.001). The subgroup of stage I patents had a median OS of 2.69 years with NAC versus 2.20 years for surgery +/- AC (Log-rank p-value < 0.001). The subgroup of stage II patients had a median OS of 2.49 years with NAC versus 1.75 years for surgery +/- AC (Log-rank p-value < 0.001). In the Cox proportional-hazards regression analyses with IPTW using propensity score matching, NAC also had a significant OS benefit for all patients (hazards ratio [HR]:0.80; 95%CI 0.78–0.83), as well as for Stage I (HR:0.89; 95%CI 0.84–0.94) and Stage II patients (HR:0.71; 95%CI 0.68–0.75) individually. The survival benefit of NAC remained when only patients that had both surgery and chemotherapy (HR:0.90; 95%CI 0.86–0.93) were evaluated. However, in this cohort, when stratified by clinical stage, NAC was only associated with an improved OS for stage II patients (HR:0.80; 95%CI 0.76–0.84) with no significant OS benefit from NAC for Stage I patients. Conclusion: NAC appears to confer a survival benefit for patients with early stage pancreatic adenocarcinoma. NAC also decreased the risk of a positive resection margin as well as positive lymph nodes at the time of surgical resection. In stage I patients that were able to receive both surgery and chemotherapy, the timing of chemotherapy did not impact survival.

The treatment sequence may matter in patients undergoing pancreatoduodenectomy for early stage pancreatic cancer in the era of modern chemotherapy

BackgroundThe aim of this study was to investigate outcomes associated with neoadjuvant chemotherapy in patients undergoing pancreatoduodenectomy for early stage pancreatic adenocarcinoma in the era of modern chemotherapy. MethodsThe National Cancer Database (2010–2016) was queried for patients with clinical stage 0–2 pancreatic adenocarcinoma who underwent pancreatoduodenectomy. Patients who underwent up-front pancreatoduodenectomy were propensity matched to patients who received neoadjuvant chemotherapy. Postoperative outcomes, pathologic outcomes, and overall survival were compared. ResultsA total of 2036 patients were in each group. Neoadjuvant chemotherapy was associated with shorter length of stay, lower 30-day readmission rate, and lower 30 and 90-day mortality rates (all p < 0.05). Neoadjuvant chemotherapy was associated with lower rates of positives nodes and positive resection margins (all p < 0.0001). Neoadjuvant chemotherapy was associated with longer survival (26.8 vs. 22.1months, p < 0.0001). Patients who received neoadjuvant chemotherapy followed by surgery and adjuvant therapy had the longest OS, followed by neoadjuvant + surgery, surgery + adjuvant therapy, and surgery alone (29.8 vs. 25.6 vs. 23.9 vs. 13.1 months; p < 0.0001). ConclusionsNeoadjuvant chemotherapy is associated with improved postoperative outcomes, oncologic outcomes, and overall survival in patients with early stage pancreatic adenocarcinoma. Neoadjuvant chemotherapy should be considered in all patients with early stage pancreatic adenocarcinoma.

Investigating disparities: the effect of social environment on pancreatic cancer survival in metastatic patients

Pancreatic adenocarcinoma (PCA) incidence is higher in Black compared to White patients. Beyond race, neighborhood socioeconomic status (nSES) may also inform disparities. However, these effects on metastatic pancreatic adenocarcinoma (mPCA) are not well-studied. The aim of this study was to explore whether nSES influences survival in patients with mPCA. nSES measures were derived from U.S. census data at the census tract (CT) level. We correlated medical records of mPCA patients (diagnosed 2010-2016; n=370) to nSES measures retrospectively via a geocode derived from patient address. Multivariable cox proportional hazards models were used to identify patient-level (age, sex, race, marital status, treatment (radiation/chemo/surgery), PCA family history, stage, Jewish ancestry, tobacco use, BMI, diabetes, and statin use) and nSES measures (deprivation, racial concentration, stability, transportation access, immigration) associated with mPCA survival; P values <0.05 were significant. Eighty-two percent of patients were White; less than one-third of patients resided in highly deprived neighborhoods. Three hundred thirty-three mPCA patient deaths occurred, with a survival ranging from 7-9 months (median 8 months). Patient-level factors including younger age, receipt of chemotherapy or initial surgery and statin use, were associated with improved survival, whereas neighborhood stability (i.e., a higher % of residents still living in the same house as 1 year ago) was significantly associated with poor pancreatic survival. Our findings suggest nSES has limited effect on survival of mPCA patients as compared to clinical variables. This may be due to the aggressive nature of this cancer, however, additional studies with larger, more diverse cohorts are needed to better understand the effect of nSES on survival of patients with mPCA.